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METROLOGICAL QUALITY FOR A BALANCE Article 1251 « Weigh with an analytical balance »
REFERENCE USP XXVIII
ARTICLE 1251 « WEIGH WITH AN ANALYTICAL BALANCE » Weighing is a frequent step in analytical procedures, and the balance is an essential piece of laboratory equipment in most analyses. In spite of this, weighing is a common source of error that can be difficult to detect in the final analytical results. The procedure described here applies directly to electronic balances; therefore, certain portions of the procedure are not applicable to other types of balance. The weighing procedure can be separated into three basic steps: planning, checking the balance, and weighing the material. Planning The initial step is to assemble the proper equipment such as containers for weighing, receiving vessels, forceps, pipets, spatulas of proper size, and so forth. Use containers of such size that the loading capacity of the balance is not exceeded. Make sure that the containers selected to receive the weighed material are clean and dry. Assemble the necessary chemicals if solutions or reagents are required. Preparation of the material to be weighed is often necessary. The material may require grinding or drying. Some materials may have been heated or stored in a refrigerator. Material must be brought to the temperature of the balance before they are weighed. To avoid condensation of moisture, refrigerated materials must be allowed to come to room temperature before the container is opened. Checking the balance In the next step it is important to that, unless the balance is checked before each weighing operation is performed, errors can easily occur, resulting in faulty analytical data. The balance should check the Balance environment, Calibration, and Balance Uncertainties. Do not assume that the balance has been left in the proper operating condition by the previous . Balance Environment The balance is placed in a suitable location with sufficiently low levels of vibration and air current. It must have a constant electrical supply. The balance and the surrounding work area have to be kept neat and tidy. It is good practice to use a camel's hair brush or its equivalent to dust the balance pan before any weighing so as to remove any materials that may have been left by the previous operator. [Note - Individuals must clean up debris, dispose of any spilled materials or paper, and remove the vessels and apparatus used in making the measurements.] When a balance is moved, it must be allowed to adjust to the temperature of its new environment and be recalibrated. Calibration If necessary turn on the power, and allow the balance to equilibrate for at least 1 hour before proceeding with the calibration. (Microbalances may require up to 24 hours reaching equilibrium.) If the balance power has gone off and then came back on, as in a power outage, certain types of balance may display a message indicating that the balance must be calibrated before a weighing is made. If the operator touches the balance bar, the message may be cleared and the balance may display zeros; however, the balance will not give the correct weighing until it has been calibrated. Chapter 22b
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Reference USP XXVIII Article 1251 « Weigh with an analytical balance » Electronic analytical balances have an internal calibration system based on an applied load. The calibration applies for the current ambient temperature. Balance Uncertainties Drift Reduction
Drift is one of the most common errors, and it is also one of the easiest to reduce or eliminate. Balance drift can be present without the operator being aware of the problem. Check the sample, the balance, and the laboratory environment for the following causes of errors, and eliminate them: (1) A balance door is open. (2) Temperatures of the balance and the material to be weighed are not the same. (3) The sample is losing or gaining weight. (4) The balance has been recently moved but has not been allowed to equilibrate to its surroundings or has not been recalibrated. (5) Air currents are present in the laboratory. (6) Temperatures in the laboratory vary. (7) The balance is not properly leveled. (8) Laboratory operations are causing vibration. (9) Hysteresis of the mechanical parts occurs during weighing. Mechanical Hysteresis
Hysteresis in the balance is caused by excessive stretching of the springs, and it is primarily due to overloading or to the accidental dropping of an object onto the pan. Microbalances are very sensitive to overload and shock. When using a microbalance, set the lever to the rest position when adding or removing material; turn the lever to the weigh position to the weight. In some cases, drift due to hysteresis can be eliminated by allowing the balance to stand without weighing long enough for it to recover. If stretching of the springs is excessive, an expensive balance overhaul may be needed. In the case of electronic force restoration balances, springs are replaced by flexures and the term creep is more appropriate than hysteresis. Quality Assurance Procedure for Measurement of Balance Drift
Over an extended period of time, balance drift and other day-to-day variations are monitored by weighing a fixed check-weight on a regular basis; this check should be performed after the balance has been calibrated at the ambient laboratory temperature. The check should be made before the first weighing of the day or after any event that might disturb the balance's calibration (power failure, moving the balance to a new location, etc.). The check-weight may be any object whose mass remains constant and does not exceed the load limit of the balance. A balance weight makes a reliable check-weight. Each balance should be provided with a check-weight, which should be stored in a protective container near the balance. Perform the following procedures to reduce balance errors and the possibility of an incorrect reading because of drift: (1) Make certain that the electrical power to the balance is on and that the level bubble is in the center of the indicator. (2) Calibrate the analytical balance or the microbalance, [Note: Some balances have a calibration lever, which must be returned fully to its original weighing position. Do not depend upon any prior calibration.] Page 2/14
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REFERENCE USP XXVIII Article 1251 « Weigh with an analytical balance » (3)
The first person to use the balance each day should weigh the checkweight and record the weight in the log book for comparison with previous readings. If a deviation greater than that indicated below for Analytical Balances and Microbalances is observed, the balance should be reported for service. [Note - Check-weights tend to gain weight upon standing because of mishandling and exposure to contaminants in the atmosphere. These weights can be cleaned by wiping with a lint-free cloth moistened with a small amount of an appropriate solvent such as diethyl ether.] Analytical balances - Select a check-weight of an appropriate mass to examine an analytical balance. If possible, set the balance to read to 5 decimal places. Follow the manufacturer's operating instructions. Pick up the check-weight with a forceps, place it carefully on the balance pan, and weigh it. [Note – Do not drop the weight on the balance pan because damage to the balance could result.] Place the weight in the center of the pan to eliminate corner weighing differences. The accuracy of the weight is not important; the only factor of interest is whether any drift has occurred. If no drift has taken place, the value should remain constant. Periodic weighing of a fixed weight will determine if the boards (or knife edges in the case of mechanical balances) in the instrument are defective. The check for drift at the most sensitive position will show if a problem exists; the variation in the observed weight does not exceed ±0.2 mg. For example, with a 20 g weight, if the mean value of the readings were 19.9984, the tolerance would be from 19.9982 to 19.9986 g. Thus, several readings must be taken before one can establish a tolerance. [Note – The check-weight need not be of high accuracy, but it is essential that its mass remain constant. In addition, the tolerance does not correspond to the value of 0.1%, specified under Weights and Balances (41), for weighing material accurately. Rather, the tolerance is purposefully tight to reveal possible drift or calibration errors: this tolerance is readily achievable with modern electronic balances. Microbalances - Proceed as directed for Analytical Balances, but use a checkweight appropriate for the particular balance. For example, a 100-mg checkweight might be selected for a balance that has a load limit of 150 mg; or a 10-mg check-weight might be used for an ultra-microbalance with a load limit of 15 mg. (The operator must know the maximum capacity of the balance to select the correct check-weight.) The balance indicates the weight in milligrams. Record the weight as soon as the reading is stable for a few seconds. The variation in weighings ought to be within a range commensurate to the specifications given by the balance manufacturer, but not greater than 0.1% of the amount of material typically weighed on the particular balance. For example, if 10-mg samples are routinely weighed, the variation in the weighings of the check-weight cannot exceed 0.01 mg. Weighing the material In this final step, select the number of decimal places required for the analytical procedure. In most pharmaceutical analyses small quantities of material are used, requiring the balance reading to be set to the fifth decimal place to achieve the necessary accuracy. Weighing read with four decimal places is preferred for weighing near-gram quantities. Do not allow the material to remain on the balance for an extended period of time because changes, caused by interaction with atmospheric water or carbon dioxide, may take place. Chapter 22b
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Reference USP XXVIII Article 1251 « Weigh with an analytical balance » Load limit Select the appropriate balance for the quantity and accuracy needed. Each balance has a load limit, which should not be exceeded. Each balance manufacturer supplies the maximum loading condition, and this limit varies with the type of balance. The operator should know this limit so that the balance will not be damaged. [NOTE - Electronic balances operate on a "load cell" principle that produces an electrical output proportional to the movement of the strain gauge and is linear over the range. Receivers The proper receiver for the material must be selected. The receiver's weight plus the weight to be measured must not exceed the maximum load for the balance: the size and shape of the receiver should be such that will permit it to fit into the space and on the balance pan without interfering with any operation. It is important that the receiver be clean and dry. Common receivers are weighing bottles, weighing funnels, flasks, and weighing paper. The correct receiver depends upon the quantity and type of material (liquid. solid. or powder) to be weighed. All other things being equal, a vessel of low mass should be chosen when small amounts of material arc to be weighed. It is recommended that gloves, forceps, or another type of gripping device be used when handling receivers, because oils from the hands will add weight. The weighing funnel is often the most satisfactory receiver, because it can function as both a weighing dish and a transfer funnel allowing easy transfer to volumetric flasks. Weighing funnels come in various sizes: the size suitable for the operation should be selected. Weighing paper may be used for solids. Paper receivers must be handled by hand, and great care must be used to prevent spills. Weighing by Difference Weighing is usually done by difference. The following methods are acceptable for good analytical results. Method 1
Tare the empty receiver as follows. Place the receiver on the balance in the center of the pan and press the appropriate tare key on the balance. This operation electrically sets the signal from the strain gauge to zero so that the weight of the receiver is no longer indicated. Add the material to the receiver, and record the weight. Transfer the weighed material to the final flask or receiver; then reweigh the original weighing receiver by placing it in the same position on the pan. [Note - Do not change the set tare of the balance between these two weighings.] The second weight represents the un-transferred material and is subtracted from the total material weight to determine the weight of the transferred material. Method 2
If the empty receiver is not going to be tared, add the material to the receiver, and place the receiver on the balance in the center of the pan. Record the weight, and transfer the weighed material to the final flask or receiver: then reweigh the original weighing receiver by returning it to the same position on the pan. The second weight represents the sum of the weights of the receiver and the untransferred material; subtract this sum from the sum of the total material weight and the receiver weight to determine the weight of the transferred material. Page 4/14
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REFERENCE USP XXVIII Article 1251 « Weigh with an analytical balance » Method 3
This method may be described as quantitative transfer. The material is added to the tared receiver; the amount is determined by difference; and then the whole amount is transferred quantitatively (e.g. by using a solvent) to the final receiver. Materials Handling Safety Procedures The operator must be familiar with precautions described in the Material safety Data Sheet for the substance before weighing it. Hazardous materials must be handled in an enclosure having appropriate air filtration. Many substances are extremely toxic, possibly allergenic, and may be liquids or finely divided particles. A mask that covers the nose and mouth should be used to prevent any inhalation of chemical dust. Gloves should be used to prevent any with the skin. [Note - The use of gloves is good practice for handling any chemical. If it is necessary to handle the container that is being weighed, the operator should put on gloves not only for self-protection but also to prevent moisture and oils from being deposited on the weighed container.] During a weighing, the operator may be exposed to high concentrations of the pure substance; therefore, the operator must carefully consider these possibilities at all times. Weighings are made on many different types of materials such as large solids, finely divided powders, and liquids (viscous or non-viscous, volatile or nonvolatile). Each type of material requires its own special handling. Weighing Solids Solids come in two forms, large chunks, with or without powdery surface, and finely divided powders or small crystals. If large chunks with a powdery surface are to be weighed, at least a piece of weighing paper must be placed on the balance pan to protect it from damage. Large non-reactive chunks that have no powdery surface may be placed directly on the pan (for example, a coated t tablet). [Note-Solid pieces must be handled with forceps, never by hand.] Static charge
Fine powders have a tendency to pick up static charge which will cause the particles to fly around. This static charge must be eliminated before a suitable weighing can be made. An antistatic device may be used to minimize this problem. [Note-Such devices may use piezoelectric components or a very small amount of a radioactive element (typically polonium) to generate a stream of ions that dissipate the static charge when ed over the powder to be weighed.] The static charge depends upon the relative humidity of the laboratory, which in turn depends upon the atmospheric conditions. In certain conditions, static charge is caused by the type of clothing worn by the operator; this charge causes large errors in the weighing when discharged. Weighing Procedure
Place the receiver on the balance pan, close the balance door, and weigh as indicated for Weighing by Difference, with the following additions. Carefully add the powdered material from a spatula until the desired amount is added. Use care to avoid spilling. Close the balance door, and record the weight as soon as the balance shows a stable reading. Spills
If solids are spilled, remove the receiver, and sweep out all of the spilled material from the balance. The spilled material must be properly disposed of and must Chapter 22b
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Reference USP XXVIII Article 1251 « Weighing on an Analytical Balances » revision draft not be swept out onto the balance table where other operators may come in with the chemical. Then either start the process over or reweigh the remaining material. [Note – Never returns any excess material to the original container. Any excess material must be disposed of in a proper manner.] Weighing Liquids Liquids may be volatile or nonvolatile and viscous or no viscous. Each type requires special attention. Weighing procedure Weigh as directed for Weighing by Difference, with the following conditions. Liquids should always be weighed into a container that can be closed so that none of the material is lost. It is best if the liquid can be added to its receiving container outside of the balance because of the possibility of a spill. [NoteLiquids spilled within the balance housing can cause serious damage to the balance, and they may be difficult to remove.) Non-viscous liquids can be handled with a Pasteur capillary pipette equipped with a small rubber bulb such as a medicine dropper bulb. The liquid is discharged into its receiver, the top is closed or stoppered, and the receiver and contents are weighed. Small quantities of viscous liquids can be handled by touching a glass stirring rod to the surface of the liquid and then carefully touching the rod to the side of the receiving vessel, which allows some of the material to be transferred. Weighing Corrosive Materials Many chemical such as salts, are corrosive, and materials of his nature should not be spilled on the balance pan or inside the balance housing. Extreme care is essential when materials of this nature are being weighed. CONCLUSION By carefully following the procedures outlined above, laboratory personnel will eliminate many errors that might be introduced into weighing procedures. However, it is important for each balance to be serviced and calibrated regularly by a specially trained internal or external service person. The balance should he tested using weights traceable to standardization by NIST. No repairs should be made to any balance by anyone other than a qualified maintenance person.
ARTICLE 1251 « WEIGHING ON AN ANALYTICAL BALANCES » REVISION DRAFT Weighing is a frequent step in analytical procedures, and the balance is an essential piece of laboratory equipment. The general information described here applies directly to electronic balances used in analytical procedures. Although many portions of the chapter are applicable to all balances, some are applicable only to this type of balance. This chapter should not be considered allinclusive, and other sources of information (e.g., the US National Institute for Science and Technology and balance manufacturers) may be useful and applicable when analysts perform a weighing operation or implement a weighing procedure. The information given in this chapter is applicable not only to balances used for materials that must be accurately weighed (see Balances <41> but also to balances used in all analytical procedures. Page 6/14
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REFERENCE USP XXVIII Article 1251 « Weighing on an Analytical Balances » revision draft QUALIFICATION
s should consult Analytical Instrument Qualification <1058>, standard operating procedures, and recommendations from manufacturers when they devise qualification plans. Installation s should consult Analytical Instrument Qualification 1058, standard operating procedures, and recommendations from manufacturers when they devise qualification plans. surface: The balance should be installed on a solid, level, nonmagnetic surface that minimizes the transmission of vibration (e.g., a floor-mounted, granite weigh bench). If a metallic surface is used, the surface should be grounded in order to prevent the buildup of static electricity. Location: If possible, the balance should be located in a room that is temperature and humidity controlled. The location should have a clean, consistent electrical power supply. The location should be free of drafts and should not be near ovens, furnaces, air conditioner ducts, or cooling fans from equipment or computers. The balance should be positioned away from outside windows so that direct sunlight does not strike the balance. The balance should not be installed near sources of electromagnetic radiation such as radio-frequency generators, electric motors, or hand-held communication devices (including cordless telephones, cellular telephones, and walkie-talkies). The balance should not be located near magnetic fields induced by laboratory instrumentation or other equipment. The performance of the balance should be assessed following installation and before use in order to demonstrate adequate performance. In some situations, it may not be possible to position the balance in an optimum environment. Examples of potential facility issues include the following: 1. Air currents sometimes are present in the laboratory. 2. Temperatures in the laboratory vary excessively (check the manufacturer’s literature about temperature sensitivity). 3. Humidity is either very low or very high. Either condition may increase the rate at which the sample weight varies because pickup or loss of water. Low humidity increases the buildup of static electricity. 4. Adjacent operations are causing vibration. 5. Corrosive materials are used nearby or are routinely weighed. 6. The balance is located within a fume hood because it is used to weigh corrosive or hazardous materials. 7. The balance is adjacent to equipment producing a magnetic field (e.g., a magnetic stirrer). 8. Direct sunlight strikes the balance. In situations when the balance is located near equipment or systems that induce vibration, drafts, electromagnetic radiation, magnetic fields, or changes in temperature or humidity, the assessment should be conducted with those systems operating in order to duplicate a worst-case scenario. Operational Qualification An operational qualification should be performed either by the or by the balance manufacturer after the equipment has been installed. As a minimum, the power should be turned on and the balance should be allowed to equiliChapter 22b
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Reference USP XXVIII Article 1251 « Weighing on an Analytical Balances » revision draft brate according to the manufacturer's instructions (1–24 h, depending on the type of balance) before use. Depending on the balance, analysts should include the following procedures in the operational qualification: 1. Mechanical mobility of all moveable parts 2. Control of stable indication 3. Manually triggered or automatic adjustment by means of built-in weights 4. Operation of ancillary equipment 5. Tare function 6. Initial calibration. Several types of electronic analytical balances use built-in weights for manually triggered or automatic adjustment. This adjustment usually is applied to reduce the drift of the balance over time and to compensate for drifts caused by variations in the ambient temperature. Calibration normally is performed as part of the operational qualification, but it also can be performed periodically thereafter. Calibration should be performed at the location where the balance is used in normal operation. Performance Qualification Table 1 provides a list of the most important balance properties that should be assessed during performance qualification. Depending on the risk of the application and the required weighing process tolerance, some of these tests may be omitted. Tests also can be omitted if there is evidence that the property in question has only minimal effect on the weighing performance. Any procedures used should be consistent with in-house standard operating procedures, applicable for the specific balance, and adequately justified. Performance qualification should be performed periodically as described in standard operating procedures, and the frequency of each of the individual tests can vary depending on the criticality of the property. The weights that are used to perform the tests should be stored and handled in a manner that minimizes contamination. Before executing the tests, the analyst should place the weights in the vicinity of the balance for an appropriate time to reach sufficient thermal equilibrium. If possible, all tests should be carried out with only one test weight in order to minimize handling errors. The tests should be recorded in such a manner that the data can be used to easily track balance performance and to assist in laboratory investigations as needed. Meaningful acceptance criteria can be set depending on the required weighing tolerance, i.e., the maximum allowed deviation permitted by specifications, regulations, etc., of a quantity to be weighed from its target value. Procedures should be in place to address test results that are outside acceptable ranges and to provide assurance that balance cleanliness and environment have not affected the result. Also, a procedure should be in place for removing a balance from operation when observed results fall outside acceptable ranges.
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REFERENCE USP XXVIII Article 1251 « Weighing on an Analytical Balances » revision draft Table 1. Suggested Performance Qualification Tests Test Definition Example Acceptance Criteria Change in weighing value divided by the change in load, usuNMT 0.05% deviaally measured beThe test load at or tion where <41> is tween zero and the sufficiently close to applicable. For other Sensitivity nominal capacity of the nominal capacity uses, respective tolthe balance. Sensitiviof the balance. erance requirement ty usually is exdivided by 2. pressed as deviation from the correct value at nominal capacity. Ability of a balance to follow the linear relationship between a NMT 0.05% deviaload and the indicattion where <41> is ed weighing value. From 3 to 6 points applicable. For other Nonlinearity usually over the range of the Linearity uses, respective tolis expressed as the balance erance requirement largest magnitude of divided by 2. any linearity deviation within the test interval. Deviation in the measurement value caused by eccentric Performed in the loading – in other center of gravity and words, the asymmetthe four quadrants rical placement of the (for rectangular plat- NMT 0.05% deviacenter of gravity of the ter shapes) or at tion where 41 is apload relative to the analogous locations plicable. For other Eccentricity load receiver. for other platter uses, respective tolEccentricity usually is erance requirement shapes. Test load expressed as the usually is between divided by 2. largest magnitude of 50% and 100% of any of the deviations the nominal capacity between an off-center of the balance. reading and the center reading for a given test load.
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Reference USP XXVIII Article 1251 « Weighing on an Analytical Balances » revision draft Test
Definition Example Acceptance Criteria Ability of a weighing instrument to display identical measurement values for repeated weighings of the same objects under the same condi10 replicate weightions, e.g., the same Requirement from ings (using a test measurement procewhere <41> is apweight that is a few Repeatability dure, same operator, plicable. For other percent of the nomisame measuring sysuses, respective tolnal capacity of the tem, same operating erance requirement. balance). conditions, and same location over a short period of time. Repeatability usually is expressed as the standard deviation of multiple weighings. Sensitivity, linearity, and eccentricity all for systematic deviations; i.e. they limit the accuracy of the balance (based on the definition of accuracy in Validation of Compendial Procedures 1225 and ICH Q2). In the International Vocabulary of Metrology (VIM) and documents of the International Organization for Standardization, this concept is referred to as trueness. Because deviations are largely independent from each other, it is not likely that all deviations occur simultaneously and have the same algebraic sign. Therefore the arithmetic addition of all individual deviations to assess the balance accuracy would constitute a rather conservative approach. A quadratic addition of the individual deviations is a more realistic approach. By allocating 50% of the weighing tolerance budget to the acceptance criteria of the individual properties, analysts ensure adherence to the required weighing tolerance. These properties – or a subset of them – also can be taken to fulfill the accuracy requirement described in <41>. In this case the acceptance criteria thus allow a maximum deviation of 0.05% for sensitivity, linearity, and eccentricity. Repeatability preferably is tested with a test weight of a few percent of the balance capacity. At the lower end of its measurement range, the performance of laboratory balances is limited by the finite repeatability, and limitations induced by systematic deviations normally can be neglected. Therefore, the whole weighing tolerance budget can be allocated to the acceptance criterion of the repeatability test. For the sensitivity and linearity tests as described above, the analyst should use certified weights with an appropriate weight class (e.g., according to International Organization of Legal Metrology R111 or American Society for Testing and Materials E617, available from and , respectively). [NOTE – If a differential method is used for the linearity test, certified weights may not be required.] Depending on the acceptance criterion, it may be sufficient to consider only the nominal weight value of the test weights. If the nominal value of the test weight is considered, analysts should ensure that the maximum permissible error Page 10/14
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REFERENCE USP XXVIII Article 1251 « Weighing on an Analytical Balances » revision draft does not exceed one-third of the acceptance criterion. Alternatively, if the certified value of the test weight is considered, its calibration uncertainty should not exceed one-third of the acceptance criterion. For tests such as eccentricity or repeatability, the use of certified weights is optional, but analysts must ensure that the mass of the weight does not change during the test. The tests described above also can be included in formal periodic calibration in order to fulfill applicable cGMP requirements. Balance Checks A balance check using an external weight helps ensuring that the balance meets weighing tolerance requirements. The balance check is performed at appropriate intervals based on applicable standard operating procedures. The frequency of the balance check depends on the risk of the application and the required weighing tolerance. Checks with external weights can be replaced partially using automatic or manually triggered adjustment by means of built-in weights. When analysts perform the balance check with an external weight, the same acceptance criteria may apply as described in the sensitivity test above. Minimum Weight The minimum net sample weight, mmin, of a balance can be expressed by the equation: mmin = k × s/required weighing tolerance where k is the coverage factor (usually 2 or larger) and s is the standard deviation (in a mass unit, e.g., in mg) of not fewer than 10 replicate measurements of a test weight. The minimum weight describes the lower limit of the balance below which the required weighing tolerance is not adhered to. The equation above takes into that the performance of laboratory balances at the lower end of the measurement range is limited by the finite repeatability. For materials that must be accurately weighed, <41> stipulates that repeatability is satisfactory if two times the standard deviation of the weighed value, divided by the nominal value of the weight used, does not exceed 0.10%. For this criterion the equation above simplifies to: mmin = 2000 × s If not subject to the requirements of <41>, the minimum weight value may vary depending on the required weighing tolerance and the specific use of the balance. To facilitate handling, the test weight that is used for the repeatability test does not need to be at the minimum weight value but can be larger because the standard deviation of repeatability is only a weak function of the test weight value. In order to satisfy the required weighing tolerance, when samples are weighed the amount of sample mass (i.e., the net weight) must be equal to or larger than the minimum weight. The minimum weight applies to the sample weight, not to the tare or gross weight. Factors that can influence repeatability while the balance is in use include: 1. The performance of the balance and thus the minimum weight can vary over time because of changing environmental conditions. 2. Different operators may weigh differently on the balance – i.e., the minimum weight determined by different operators may be different. 3. The standard deviation of a finite number of replicate weighings is only an estimation of the true standard deviation, which is unknown. 4. The determination of the minimum weight with a test weight may not be completely representative for the weighing application. Chapter 22b
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Reference USP XXVIII Article 1251 « Weighing on an Analytical Balances » revision draft 5. The tare vessel also may influence minimum weight because of the interaction of the environment with the surface of the tare vessel. For these reasons, when possible, weighings should be made at larger values than the minimum weight. OPERATION OF THE ANALYTICAL BALANCE Select the appropriate balance for the quantity and performance needed. General chapter <41> provides requirements for balances used for materials that must be accurately weighed. The balance should check the balance environment (vibration, air currents, and cleanliness) and status of calibration before use. Receivers To ensure suitable performance in measuring the weight of a specimen, analysts should consider selection of a proper receiver for the material. General characteristics: All receivers must be clean, dry, and inert. The total weight of the receiver plus the specimen must not exceed the maximum capacity of the balance. With a properly maintained and adjusted laboratory balance, weighing uncertainty for small samples, i.e., net weights with a mass not exceeding typically a few percent of the capacity of the balance, essentially is determined by the repeatability. However, repeatability depends on the size and surface area of the weighed object. For this reason large or heavy receivers introduce a deviation from the conditions under which the repeatability was determined without considering the receivers. Therefore, either receivers of a low mass and small surface should be used (especially in cases when specimens of low weight are being measured) or the repeatability test should be performed with the receiver placed on the weighing pan as a preload. Receivers should be constructed from nonmagnetic materials in order to prevent magnetic interference with electronic balance components. Receivers should be used at ambient temperature in order to prevent the formation of air currents within the weighing chamber. Solid samples: Receivers for weighing solid materials include weighing paper, weighing dishes, weighing funnels, or enclosed vessels, including bottles, vials, and flasks. Hygroscopic papers are not recommended for weighing because they may have a detrimental effect on the observed results. Weighing dishes typically are constructed from a polymer or from aluminum. Antistatic weighing dishes are available for measuring materials that retain static electricity. Weighing funnels typically are constructed from glass or from a polymer. The design of this type of receiver combines attributes of a weighing dish and a transfer funnel, which can simplify the analytical transfer of a weighed powder to a narrow-necked vessel such as a volumetric flask. For solid samples that are volatile or deliquescent, analysts must weigh the material into an enclosed vessel. Where practical, analysts should use an enclosed vessel with a small opening in order to reduce sample weight loss from volatilization or weight gain from the adsorption and absorption of atmospheric water. Liquid samples: Receivers for liquid samples typically are inert, enclosed vessels. For liquid samples that are volatile or deliquescent, analysts should use an enclosed vessel with a small opening, and the enclosure should be replaced rapidly following material transfer. Special precautions should be taken Page 12/14
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REFERENCE USP XXVIII Article 1251 « Weighing on an Analytical Balances » revision draft to be certain that the receiver and the enclosure are constructed from a material that is compatible with the liquid sample. The receiver and enclosure must have a seal that is sufficient to prevent leaks from a liquid that is of low viscosity or has low surface tension or a low boiling point. Types of Weighing Weighing for quantitative analysis: The initial step for many quantitative analyses is to accurately weigh a specified amount of a sample. Section 6.50.20 in the General Notices stipulates that solutions for quantitative measures must be prepared using accurately weighed analytes: i.e., analysts must follow <41>. Errors introduced during the weighing of a sample can affect the accuracy of all subsequent analytical measurements. Addition weighing: Addition weighings typically are used for solid samples or liquid samples for which volatility is not an issue. The receiver is placed on the balance. After the balance display stabilizes, the analyst should tare the balance; add the desired amount of material to the receiver; allow the balance display to stabilize; record the weight; and quantitatively transfer the material to an appropriate vessel or, if it cannot be guaranteed that the entire amount has been transferred, weigh the receiver again and note the weight difference. Dispense weighing: Dispense weighing typically is used for weighing emulsions or viscous liquids such as topical ointments. In these situations it is not practical to weigh the material into a typical receiver. Accordingly, the analyst should tare the balance; place the sample on the balance in a suitable container (e.g., a bottle, tube, transfer pipette, or syringe) that has been wiped clean on the outside; record the weight after the balance display stabilizes; transfer the desired amount of sample to an appropriate receiving vessel, such as a volumetric flask; and place the pipette or syringe back onto the balance. The difference in the two weighings is equal to the weight of the transferred specimen. Gravimetric dosing: Gravimetric dosing typically is used for sample and standard preparations or capsule filling. For such weighing the analyst places the volumetric flask, vial, or capsule shell on the balance; tares the balance after the balance display stabilizes; adds the solid or liquid components into the receiver by means of dosing units; and records the respective weights. Problem Samples Electrically charged samples and receivers: Dry, finely divided powders may be charged with static electricity that can make the powder either attracted to or repelled by the receiver or the balance, causing inaccurate weight measurements and specimen loss during transfer. A drift in the balance readings should alert the operator to the possibility that the material has a static charge. Commercially available balances with a built-in antistatic device can be used to remedy the problem. Such devices may use piezoelectric components or a very small amount of a radioactive element (typically polonium) to generate a stream of ions that dissipate the static charge when ed over the powder being weighed. Antistatic weigh boats, antistatic guns, and antistatic screens also are commercially available. The static charge depends also on the relative humidity of the laboratory, which in turn depends on atmospheric conditions. Under certain conditions, static charge is caused by the type of clothing worn by the operator and this charge can cause large errors in the weighing. Borosilicate glassware and plastic receivers have a well-known propensity for picking Chapter 22b
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Reference USP XXVIII Article 1251 « Weighing on an Analytical Balances » revision draft up static charge, especially at low relative humidity. The gloves used to protect the operator also may increase the potential for a static charge problem. Placing the container in a metal holder may help to shield the static charge, and antistatic gloves also can help to alleviate the problem. Volatile samples: When weighing a liquid that has a low boiling point, analysts must receive the specimen in a vessel with a gas-tight enclosure of small diameter. The analyst then tares the vessel and enclosure, adds the desired amount of sample, and replaces the enclosure. After the balance display stabilizes, the analyst records the specimen weight. Warm or cool samples: Samples that are warm or cool should be equilibrated in the laboratory, or the weight readings may be erroneous. With regard to warm samples, the apparent weight is smaller than the true weight because of heat convection. For example, a flask that is warmer than ambient air warms up this air, which then flows upward along the flask and reduces the apparent weight of the contents by viscous friction. Hygroscopic samples: Hygroscopic materials readily absorb moisture from the atmosphere and steadily gain weight if left exposed. Therefore, hygroscopic samples must be either weighed promptly or placed in a vessel with a gas-tight enclosure. For a gas-tight vessel, analysts should tare the vessel and enclosure, add the desired amount of sample, and replace the enclosure. After the balance display stabilizes, the analyst can record the specimen weight. Aseptic or biohazardous samples: The weighing of sterile or biohazardous samples should take place within the confines of a clean bench, biosafety cabinet, isolator, or similar containment device. Air flow within the hood potentially can cause balance instability, so after a balance has been installed under a hood, analysts should perform a rigorous qualification study with suitable weight artifacts (see <41>) in order to determine the acceptability of the balance performance in this environment. Weighing corrosive materials: Many chemicals, such as salts, are corrosive, and materials of this nature should not be spilled on the balance pan or inside the balance housing. Extra care is essential when materials of this nature are weighed. Analysts should consider the use of sealed containers such as weighing bottles or syringes. In the event of a spill, requalification of balance may be necessary, depending on the nature of the spill. Safety Considerations When Weighing During a weighing, the analyst may be exposed to high concentrations of a pure substance. The analyst must carefully consider this possibility at all times and should be familiar with the precautions described in the substance′ s Material Safety Data Sheet before weighing it. Hazardous materials should be handled in an enclosure that has appropriate air filtration. Many toxic – and possibly allergenic – substances present as liquids or finely divided particles. When weighing these substances, analysts should use a mask that covers the nose and mouth to prevent any inhalation of the substance, and they should use gloves to prevent any with the skin. [NOTE – The use of gloves is good practice for handling any chemical. If it is necessary to handle the container being weighed, the analyst should wear gloves not only for self-protection but also to prevent moisture and oils from being deposited on the weighed container.]
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Chapter 22b
22b
METROLOGICAL QUALITY FOR A BALANCE Article 1251 « Weigh with an analytical balance »
REFERENCE USP XXVIII
ARTICLE 1251 « WEIGH WITH AN ANALYTICAL BALANCE » Weighing is a frequent step in analytical procedures, and the balance is an essential piece of laboratory equipment in most analyses. In spite of this, weighing is a common source of error that can be difficult to detect in the final analytical results. The procedure described here applies directly to electronic balances; therefore, certain portions of the procedure are not applicable to other types of balance. The weighing procedure can be separated into three basic steps: planning, checking the balance, and weighing the material. Planning The initial step is to assemble the proper equipment such as containers for weighing, receiving vessels, forceps, pipets, spatulas of proper size, and so forth. Use containers of such size that the loading capacity of the balance is not exceeded. Make sure that the containers selected to receive the weighed material are clean and dry. Assemble the necessary chemicals if solutions or reagents are required. Preparation of the material to be weighed is often necessary. The material may require grinding or drying. Some materials may have been heated or stored in a refrigerator. Material must be brought to the temperature of the balance before they are weighed. To avoid condensation of moisture, refrigerated materials must be allowed to come to room temperature before the container is opened. Checking the balance In the next step it is important to that, unless the balance is checked before each weighing operation is performed, errors can easily occur, resulting in faulty analytical data. The balance should check the Balance environment, Calibration, and Balance Uncertainties. Do not assume that the balance has been left in the proper operating condition by the previous . Balance Environment The balance is placed in a suitable location with sufficiently low levels of vibration and air current. It must have a constant electrical supply. The balance and the surrounding work area have to be kept neat and tidy. It is good practice to use a camel's hair brush or its equivalent to dust the balance pan before any weighing so as to remove any materials that may have been left by the previous operator. [Note - Individuals must clean up debris, dispose of any spilled materials or paper, and remove the vessels and apparatus used in making the measurements.] When a balance is moved, it must be allowed to adjust to the temperature of its new environment and be recalibrated. Calibration If necessary turn on the power, and allow the balance to equilibrate for at least 1 hour before proceeding with the calibration. (Microbalances may require up to 24 hours reaching equilibrium.) If the balance power has gone off and then came back on, as in a power outage, certain types of balance may display a message indicating that the balance must be calibrated before a weighing is made. If the operator touches the balance bar, the message may be cleared and the balance may display zeros; however, the balance will not give the correct weighing until it has been calibrated. Chapter 22b
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Reference USP XXVIII Article 1251 « Weigh with an analytical balance » Electronic analytical balances have an internal calibration system based on an applied load. The calibration applies for the current ambient temperature. Balance Uncertainties Drift Reduction
Drift is one of the most common errors, and it is also one of the easiest to reduce or eliminate. Balance drift can be present without the operator being aware of the problem. Check the sample, the balance, and the laboratory environment for the following causes of errors, and eliminate them: (1) A balance door is open. (2) Temperatures of the balance and the material to be weighed are not the same. (3) The sample is losing or gaining weight. (4) The balance has been recently moved but has not been allowed to equilibrate to its surroundings or has not been recalibrated. (5) Air currents are present in the laboratory. (6) Temperatures in the laboratory vary. (7) The balance is not properly leveled. (8) Laboratory operations are causing vibration. (9) Hysteresis of the mechanical parts occurs during weighing. Mechanical Hysteresis
Hysteresis in the balance is caused by excessive stretching of the springs, and it is primarily due to overloading or to the accidental dropping of an object onto the pan. Microbalances are very sensitive to overload and shock. When using a microbalance, set the lever to the rest position when adding or removing material; turn the lever to the weigh position to the weight. In some cases, drift due to hysteresis can be eliminated by allowing the balance to stand without weighing long enough for it to recover. If stretching of the springs is excessive, an expensive balance overhaul may be needed. In the case of electronic force restoration balances, springs are replaced by flexures and the term creep is more appropriate than hysteresis. Quality Assurance Procedure for Measurement of Balance Drift
Over an extended period of time, balance drift and other day-to-day variations are monitored by weighing a fixed check-weight on a regular basis; this check should be performed after the balance has been calibrated at the ambient laboratory temperature. The check should be made before the first weighing of the day or after any event that might disturb the balance's calibration (power failure, moving the balance to a new location, etc.). The check-weight may be any object whose mass remains constant and does not exceed the load limit of the balance. A balance weight makes a reliable check-weight. Each balance should be provided with a check-weight, which should be stored in a protective container near the balance. Perform the following procedures to reduce balance errors and the possibility of an incorrect reading because of drift: (1) Make certain that the electrical power to the balance is on and that the level bubble is in the center of the indicator. (2) Calibrate the analytical balance or the microbalance, [Note: Some balances have a calibration lever, which must be returned fully to its original weighing position. Do not depend upon any prior calibration.] Page 2/14
Chapter 22b
REFERENCE USP XXVIII Article 1251 « Weigh with an analytical balance » (3)
The first person to use the balance each day should weigh the checkweight and record the weight in the log book for comparison with previous readings. If a deviation greater than that indicated below for Analytical Balances and Microbalances is observed, the balance should be reported for service. [Note - Check-weights tend to gain weight upon standing because of mishandling and exposure to contaminants in the atmosphere. These weights can be cleaned by wiping with a lint-free cloth moistened with a small amount of an appropriate solvent such as diethyl ether.] Analytical balances - Select a check-weight of an appropriate mass to examine an analytical balance. If possible, set the balance to read to 5 decimal places. Follow the manufacturer's operating instructions. Pick up the check-weight with a forceps, place it carefully on the balance pan, and weigh it. [Note – Do not drop the weight on the balance pan because damage to the balance could result.] Place the weight in the center of the pan to eliminate corner weighing differences. The accuracy of the weight is not important; the only factor of interest is whether any drift has occurred. If no drift has taken place, the value should remain constant. Periodic weighing of a fixed weight will determine if the boards (or knife edges in the case of mechanical balances) in the instrument are defective. The check for drift at the most sensitive position will show if a problem exists; the variation in the observed weight does not exceed ±0.2 mg. For example, with a 20 g weight, if the mean value of the readings were 19.9984, the tolerance would be from 19.9982 to 19.9986 g. Thus, several readings must be taken before one can establish a tolerance. [Note – The check-weight need not be of high accuracy, but it is essential that its mass remain constant. In addition, the tolerance does not correspond to the value of 0.1%, specified under Weights and Balances (41), for weighing material accurately. Rather, the tolerance is purposefully tight to reveal possible drift or calibration errors: this tolerance is readily achievable with modern electronic balances. Microbalances - Proceed as directed for Analytical Balances, but use a checkweight appropriate for the particular balance. For example, a 100-mg checkweight might be selected for a balance that has a load limit of 150 mg; or a 10-mg check-weight might be used for an ultra-microbalance with a load limit of 15 mg. (The operator must know the maximum capacity of the balance to select the correct check-weight.) The balance indicates the weight in milligrams. Record the weight as soon as the reading is stable for a few seconds. The variation in weighings ought to be within a range commensurate to the specifications given by the balance manufacturer, but not greater than 0.1% of the amount of material typically weighed on the particular balance. For example, if 10-mg samples are routinely weighed, the variation in the weighings of the check-weight cannot exceed 0.01 mg. Weighing the material In this final step, select the number of decimal places required for the analytical procedure. In most pharmaceutical analyses small quantities of material are used, requiring the balance reading to be set to the fifth decimal place to achieve the necessary accuracy. Weighing read with four decimal places is preferred for weighing near-gram quantities. Do not allow the material to remain on the balance for an extended period of time because changes, caused by interaction with atmospheric water or carbon dioxide, may take place. Chapter 22b
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Reference USP XXVIII Article 1251 « Weigh with an analytical balance » Load limit Select the appropriate balance for the quantity and accuracy needed. Each balance has a load limit, which should not be exceeded. Each balance manufacturer supplies the maximum loading condition, and this limit varies with the type of balance. The operator should know this limit so that the balance will not be damaged. [NOTE - Electronic balances operate on a "load cell" principle that produces an electrical output proportional to the movement of the strain gauge and is linear over the range. Receivers The proper receiver for the material must be selected. The receiver's weight plus the weight to be measured must not exceed the maximum load for the balance: the size and shape of the receiver should be such that will permit it to fit into the space and on the balance pan without interfering with any operation. It is important that the receiver be clean and dry. Common receivers are weighing bottles, weighing funnels, flasks, and weighing paper. The correct receiver depends upon the quantity and type of material (liquid. solid. or powder) to be weighed. All other things being equal, a vessel of low mass should be chosen when small amounts of material arc to be weighed. It is recommended that gloves, forceps, or another type of gripping device be used when handling receivers, because oils from the hands will add weight. The weighing funnel is often the most satisfactory receiver, because it can function as both a weighing dish and a transfer funnel allowing easy transfer to volumetric flasks. Weighing funnels come in various sizes: the size suitable for the operation should be selected. Weighing paper may be used for solids. Paper receivers must be handled by hand, and great care must be used to prevent spills. Weighing by Difference Weighing is usually done by difference. The following methods are acceptable for good analytical results. Method 1
Tare the empty receiver as follows. Place the receiver on the balance in the center of the pan and press the appropriate tare key on the balance. This operation electrically sets the signal from the strain gauge to zero so that the weight of the receiver is no longer indicated. Add the material to the receiver, and record the weight. Transfer the weighed material to the final flask or receiver; then reweigh the original weighing receiver by placing it in the same position on the pan. [Note - Do not change the set tare of the balance between these two weighings.] The second weight represents the un-transferred material and is subtracted from the total material weight to determine the weight of the transferred material. Method 2
If the empty receiver is not going to be tared, add the material to the receiver, and place the receiver on the balance in the center of the pan. Record the weight, and transfer the weighed material to the final flask or receiver: then reweigh the original weighing receiver by returning it to the same position on the pan. The second weight represents the sum of the weights of the receiver and the untransferred material; subtract this sum from the sum of the total material weight and the receiver weight to determine the weight of the transferred material. Page 4/14
Chapter 22b
REFERENCE USP XXVIII Article 1251 « Weigh with an analytical balance » Method 3
This method may be described as quantitative transfer. The material is added to the tared receiver; the amount is determined by difference; and then the whole amount is transferred quantitatively (e.g. by using a solvent) to the final receiver. Materials Handling Safety Procedures The operator must be familiar with precautions described in the Material safety Data Sheet for the substance before weighing it. Hazardous materials must be handled in an enclosure having appropriate air filtration. Many substances are extremely toxic, possibly allergenic, and may be liquids or finely divided particles. A mask that covers the nose and mouth should be used to prevent any inhalation of chemical dust. Gloves should be used to prevent any with the skin. [Note - The use of gloves is good practice for handling any chemical. If it is necessary to handle the container that is being weighed, the operator should put on gloves not only for self-protection but also to prevent moisture and oils from being deposited on the weighed container.] During a weighing, the operator may be exposed to high concentrations of the pure substance; therefore, the operator must carefully consider these possibilities at all times. Weighings are made on many different types of materials such as large solids, finely divided powders, and liquids (viscous or non-viscous, volatile or nonvolatile). Each type of material requires its own special handling. Weighing Solids Solids come in two forms, large chunks, with or without powdery surface, and finely divided powders or small crystals. If large chunks with a powdery surface are to be weighed, at least a piece of weighing paper must be placed on the balance pan to protect it from damage. Large non-reactive chunks that have no powdery surface may be placed directly on the pan (for example, a coated t tablet). [Note-Solid pieces must be handled with forceps, never by hand.] Static charge
Fine powders have a tendency to pick up static charge which will cause the particles to fly around. This static charge must be eliminated before a suitable weighing can be made. An antistatic device may be used to minimize this problem. [Note-Such devices may use piezoelectric components or a very small amount of a radioactive element (typically polonium) to generate a stream of ions that dissipate the static charge when ed over the powder to be weighed.] The static charge depends upon the relative humidity of the laboratory, which in turn depends upon the atmospheric conditions. In certain conditions, static charge is caused by the type of clothing worn by the operator; this charge causes large errors in the weighing when discharged. Weighing Procedure
Place the receiver on the balance pan, close the balance door, and weigh as indicated for Weighing by Difference, with the following additions. Carefully add the powdered material from a spatula until the desired amount is added. Use care to avoid spilling. Close the balance door, and record the weight as soon as the balance shows a stable reading. Spills
If solids are spilled, remove the receiver, and sweep out all of the spilled material from the balance. The spilled material must be properly disposed of and must Chapter 22b
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Reference USP XXVIII Article 1251 « Weighing on an Analytical Balances » revision draft not be swept out onto the balance table where other operators may come in with the chemical. Then either start the process over or reweigh the remaining material. [Note – Never returns any excess material to the original container. Any excess material must be disposed of in a proper manner.] Weighing Liquids Liquids may be volatile or nonvolatile and viscous or no viscous. Each type requires special attention. Weighing procedure Weigh as directed for Weighing by Difference, with the following conditions. Liquids should always be weighed into a container that can be closed so that none of the material is lost. It is best if the liquid can be added to its receiving container outside of the balance because of the possibility of a spill. [NoteLiquids spilled within the balance housing can cause serious damage to the balance, and they may be difficult to remove.) Non-viscous liquids can be handled with a Pasteur capillary pipette equipped with a small rubber bulb such as a medicine dropper bulb. The liquid is discharged into its receiver, the top is closed or stoppered, and the receiver and contents are weighed. Small quantities of viscous liquids can be handled by touching a glass stirring rod to the surface of the liquid and then carefully touching the rod to the side of the receiving vessel, which allows some of the material to be transferred. Weighing Corrosive Materials Many chemical such as salts, are corrosive, and materials of his nature should not be spilled on the balance pan or inside the balance housing. Extreme care is essential when materials of this nature are being weighed. CONCLUSION By carefully following the procedures outlined above, laboratory personnel will eliminate many errors that might be introduced into weighing procedures. However, it is important for each balance to be serviced and calibrated regularly by a specially trained internal or external service person. The balance should he tested using weights traceable to standardization by NIST. No repairs should be made to any balance by anyone other than a qualified maintenance person.
ARTICLE 1251 « WEIGHING ON AN ANALYTICAL BALANCES » REVISION DRAFT Weighing is a frequent step in analytical procedures, and the balance is an essential piece of laboratory equipment. The general information described here applies directly to electronic balances used in analytical procedures. Although many portions of the chapter are applicable to all balances, some are applicable only to this type of balance. This chapter should not be considered allinclusive, and other sources of information (e.g., the US National Institute for Science and Technology and balance manufacturers) may be useful and applicable when analysts perform a weighing operation or implement a weighing procedure. The information given in this chapter is applicable not only to balances used for materials that must be accurately weighed (see Balances <41> but also to balances used in all analytical procedures. Page 6/14
Chapter 22b
REFERENCE USP XXVIII Article 1251 « Weighing on an Analytical Balances » revision draft QUALIFICATION
s should consult Analytical Instrument Qualification <1058>, standard operating procedures, and recommendations from manufacturers when they devise qualification plans. Installation s should consult Analytical Instrument Qualification 1058, standard operating procedures, and recommendations from manufacturers when they devise qualification plans. surface: The balance should be installed on a solid, level, nonmagnetic surface that minimizes the transmission of vibration (e.g., a floor-mounted, granite weigh bench). If a metallic surface is used, the surface should be grounded in order to prevent the buildup of static electricity. Location: If possible, the balance should be located in a room that is temperature and humidity controlled. The location should have a clean, consistent electrical power supply. The location should be free of drafts and should not be near ovens, furnaces, air conditioner ducts, or cooling fans from equipment or computers. The balance should be positioned away from outside windows so that direct sunlight does not strike the balance. The balance should not be installed near sources of electromagnetic radiation such as radio-frequency generators, electric motors, or hand-held communication devices (including cordless telephones, cellular telephones, and walkie-talkies). The balance should not be located near magnetic fields induced by laboratory instrumentation or other equipment. The performance of the balance should be assessed following installation and before use in order to demonstrate adequate performance. In some situations, it may not be possible to position the balance in an optimum environment. Examples of potential facility issues include the following: 1. Air currents sometimes are present in the laboratory. 2. Temperatures in the laboratory vary excessively (check the manufacturer’s literature about temperature sensitivity). 3. Humidity is either very low or very high. Either condition may increase the rate at which the sample weight varies because pickup or loss of water. Low humidity increases the buildup of static electricity. 4. Adjacent operations are causing vibration. 5. Corrosive materials are used nearby or are routinely weighed. 6. The balance is located within a fume hood because it is used to weigh corrosive or hazardous materials. 7. The balance is adjacent to equipment producing a magnetic field (e.g., a magnetic stirrer). 8. Direct sunlight strikes the balance. In situations when the balance is located near equipment or systems that induce vibration, drafts, electromagnetic radiation, magnetic fields, or changes in temperature or humidity, the assessment should be conducted with those systems operating in order to duplicate a worst-case scenario. Operational Qualification An operational qualification should be performed either by the or by the balance manufacturer after the equipment has been installed. As a minimum, the power should be turned on and the balance should be allowed to equiliChapter 22b
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Reference USP XXVIII Article 1251 « Weighing on an Analytical Balances » revision draft brate according to the manufacturer's instructions (1–24 h, depending on the type of balance) before use. Depending on the balance, analysts should include the following procedures in the operational qualification: 1. Mechanical mobility of all moveable parts 2. Control of stable indication 3. Manually triggered or automatic adjustment by means of built-in weights 4. Operation of ancillary equipment 5. Tare function 6. Initial calibration. Several types of electronic analytical balances use built-in weights for manually triggered or automatic adjustment. This adjustment usually is applied to reduce the drift of the balance over time and to compensate for drifts caused by variations in the ambient temperature. Calibration normally is performed as part of the operational qualification, but it also can be performed periodically thereafter. Calibration should be performed at the location where the balance is used in normal operation. Performance Qualification Table 1 provides a list of the most important balance properties that should be assessed during performance qualification. Depending on the risk of the application and the required weighing process tolerance, some of these tests may be omitted. Tests also can be omitted if there is evidence that the property in question has only minimal effect on the weighing performance. Any procedures used should be consistent with in-house standard operating procedures, applicable for the specific balance, and adequately justified. Performance qualification should be performed periodically as described in standard operating procedures, and the frequency of each of the individual tests can vary depending on the criticality of the property. The weights that are used to perform the tests should be stored and handled in a manner that minimizes contamination. Before executing the tests, the analyst should place the weights in the vicinity of the balance for an appropriate time to reach sufficient thermal equilibrium. If possible, all tests should be carried out with only one test weight in order to minimize handling errors. The tests should be recorded in such a manner that the data can be used to easily track balance performance and to assist in laboratory investigations as needed. Meaningful acceptance criteria can be set depending on the required weighing tolerance, i.e., the maximum allowed deviation permitted by specifications, regulations, etc., of a quantity to be weighed from its target value. Procedures should be in place to address test results that are outside acceptable ranges and to provide assurance that balance cleanliness and environment have not affected the result. Also, a procedure should be in place for removing a balance from operation when observed results fall outside acceptable ranges.
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Chapter 22b
REFERENCE USP XXVIII Article 1251 « Weighing on an Analytical Balances » revision draft Table 1. Suggested Performance Qualification Tests Test Definition Example Acceptance Criteria Change in weighing value divided by the change in load, usuNMT 0.05% deviaally measured beThe test load at or tion where <41> is tween zero and the sufficiently close to applicable. For other Sensitivity nominal capacity of the nominal capacity uses, respective tolthe balance. Sensitiviof the balance. erance requirement ty usually is exdivided by 2. pressed as deviation from the correct value at nominal capacity. Ability of a balance to follow the linear relationship between a NMT 0.05% deviaload and the indicattion where <41> is ed weighing value. From 3 to 6 points applicable. For other Nonlinearity usually over the range of the Linearity uses, respective tolis expressed as the balance erance requirement largest magnitude of divided by 2. any linearity deviation within the test interval. Deviation in the measurement value caused by eccentric Performed in the loading – in other center of gravity and words, the asymmetthe four quadrants rical placement of the (for rectangular plat- NMT 0.05% deviacenter of gravity of the ter shapes) or at tion where 41 is apload relative to the analogous locations plicable. For other Eccentricity load receiver. for other platter uses, respective tolEccentricity usually is erance requirement shapes. Test load expressed as the usually is between divided by 2. largest magnitude of 50% and 100% of any of the deviations the nominal capacity between an off-center of the balance. reading and the center reading for a given test load.
Chapter 22b
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Reference USP XXVIII Article 1251 « Weighing on an Analytical Balances » revision draft Test
Definition Example Acceptance Criteria Ability of a weighing instrument to display identical measurement values for repeated weighings of the same objects under the same condi10 replicate weightions, e.g., the same Requirement from ings (using a test measurement procewhere <41> is apweight that is a few Repeatability dure, same operator, plicable. For other percent of the nomisame measuring sysuses, respective tolnal capacity of the tem, same operating erance requirement. balance). conditions, and same location over a short period of time. Repeatability usually is expressed as the standard deviation of multiple weighings. Sensitivity, linearity, and eccentricity all for systematic deviations; i.e. they limit the accuracy of the balance (based on the definition of accuracy in Validation of Compendial Procedures 1225 and ICH Q2). In the International Vocabulary of Metrology (VIM) and documents of the International Organization for Standardization, this concept is referred to as trueness. Because deviations are largely independent from each other, it is not likely that all deviations occur simultaneously and have the same algebraic sign. Therefore the arithmetic addition of all individual deviations to assess the balance accuracy would constitute a rather conservative approach. A quadratic addition of the individual deviations is a more realistic approach. By allocating 50% of the weighing tolerance budget to the acceptance criteria of the individual properties, analysts ensure adherence to the required weighing tolerance. These properties – or a subset of them – also can be taken to fulfill the accuracy requirement described in <41>. In this case the acceptance criteria thus allow a maximum deviation of 0.05% for sensitivity, linearity, and eccentricity. Repeatability preferably is tested with a test weight of a few percent of the balance capacity. At the lower end of its measurement range, the performance of laboratory balances is limited by the finite repeatability, and limitations induced by systematic deviations normally can be neglected. Therefore, the whole weighing tolerance budget can be allocated to the acceptance criterion of the repeatability test. For the sensitivity and linearity tests as described above, the analyst should use certified weights with an appropriate weight class (e.g., according to International Organization of Legal Metrology R111 or American Society for Testing and Materials E617, available from and , respectively). [NOTE – If a differential method is used for the linearity test, certified weights may not be required.] Depending on the acceptance criterion, it may be sufficient to consider only the nominal weight value of the test weights. If the nominal value of the test weight is considered, analysts should ensure that the maximum permissible error Page 10/14
Chapter 22b
REFERENCE USP XXVIII Article 1251 « Weighing on an Analytical Balances » revision draft does not exceed one-third of the acceptance criterion. Alternatively, if the certified value of the test weight is considered, its calibration uncertainty should not exceed one-third of the acceptance criterion. For tests such as eccentricity or repeatability, the use of certified weights is optional, but analysts must ensure that the mass of the weight does not change during the test. The tests described above also can be included in formal periodic calibration in order to fulfill applicable cGMP requirements. Balance Checks A balance check using an external weight helps ensuring that the balance meets weighing tolerance requirements. The balance check is performed at appropriate intervals based on applicable standard operating procedures. The frequency of the balance check depends on the risk of the application and the required weighing tolerance. Checks with external weights can be replaced partially using automatic or manually triggered adjustment by means of built-in weights. When analysts perform the balance check with an external weight, the same acceptance criteria may apply as described in the sensitivity test above. Minimum Weight The minimum net sample weight, mmin, of a balance can be expressed by the equation: mmin = k × s/required weighing tolerance where k is the coverage factor (usually 2 or larger) and s is the standard deviation (in a mass unit, e.g., in mg) of not fewer than 10 replicate measurements of a test weight. The minimum weight describes the lower limit of the balance below which the required weighing tolerance is not adhered to. The equation above takes into that the performance of laboratory balances at the lower end of the measurement range is limited by the finite repeatability. For materials that must be accurately weighed, <41> stipulates that repeatability is satisfactory if two times the standard deviation of the weighed value, divided by the nominal value of the weight used, does not exceed 0.10%. For this criterion the equation above simplifies to: mmin = 2000 × s If not subject to the requirements of <41>, the minimum weight value may vary depending on the required weighing tolerance and the specific use of the balance. To facilitate handling, the test weight that is used for the repeatability test does not need to be at the minimum weight value but can be larger because the standard deviation of repeatability is only a weak function of the test weight value. In order to satisfy the required weighing tolerance, when samples are weighed the amount of sample mass (i.e., the net weight) must be equal to or larger than the minimum weight. The minimum weight applies to the sample weight, not to the tare or gross weight. Factors that can influence repeatability while the balance is in use include: 1. The performance of the balance and thus the minimum weight can vary over time because of changing environmental conditions. 2. Different operators may weigh differently on the balance – i.e., the minimum weight determined by different operators may be different. 3. The standard deviation of a finite number of replicate weighings is only an estimation of the true standard deviation, which is unknown. 4. The determination of the minimum weight with a test weight may not be completely representative for the weighing application. Chapter 22b
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Reference USP XXVIII Article 1251 « Weighing on an Analytical Balances » revision draft 5. The tare vessel also may influence minimum weight because of the interaction of the environment with the surface of the tare vessel. For these reasons, when possible, weighings should be made at larger values than the minimum weight. OPERATION OF THE ANALYTICAL BALANCE Select the appropriate balance for the quantity and performance needed. General chapter <41> provides requirements for balances used for materials that must be accurately weighed. The balance should check the balance environment (vibration, air currents, and cleanliness) and status of calibration before use. Receivers To ensure suitable performance in measuring the weight of a specimen, analysts should consider selection of a proper receiver for the material. General characteristics: All receivers must be clean, dry, and inert. The total weight of the receiver plus the specimen must not exceed the maximum capacity of the balance. With a properly maintained and adjusted laboratory balance, weighing uncertainty for small samples, i.e., net weights with a mass not exceeding typically a few percent of the capacity of the balance, essentially is determined by the repeatability. However, repeatability depends on the size and surface area of the weighed object. For this reason large or heavy receivers introduce a deviation from the conditions under which the repeatability was determined without considering the receivers. Therefore, either receivers of a low mass and small surface should be used (especially in cases when specimens of low weight are being measured) or the repeatability test should be performed with the receiver placed on the weighing pan as a preload. Receivers should be constructed from nonmagnetic materials in order to prevent magnetic interference with electronic balance components. Receivers should be used at ambient temperature in order to prevent the formation of air currents within the weighing chamber. Solid samples: Receivers for weighing solid materials include weighing paper, weighing dishes, weighing funnels, or enclosed vessels, including bottles, vials, and flasks. Hygroscopic papers are not recommended for weighing because they may have a detrimental effect on the observed results. Weighing dishes typically are constructed from a polymer or from aluminum. Antistatic weighing dishes are available for measuring materials that retain static electricity. Weighing funnels typically are constructed from glass or from a polymer. The design of this type of receiver combines attributes of a weighing dish and a transfer funnel, which can simplify the analytical transfer of a weighed powder to a narrow-necked vessel such as a volumetric flask. For solid samples that are volatile or deliquescent, analysts must weigh the material into an enclosed vessel. Where practical, analysts should use an enclosed vessel with a small opening in order to reduce sample weight loss from volatilization or weight gain from the adsorption and absorption of atmospheric water. Liquid samples: Receivers for liquid samples typically are inert, enclosed vessels. For liquid samples that are volatile or deliquescent, analysts should use an enclosed vessel with a small opening, and the enclosure should be replaced rapidly following material transfer. Special precautions should be taken Page 12/14
Chapter 22b
REFERENCE USP XXVIII Article 1251 « Weighing on an Analytical Balances » revision draft to be certain that the receiver and the enclosure are constructed from a material that is compatible with the liquid sample. The receiver and enclosure must have a seal that is sufficient to prevent leaks from a liquid that is of low viscosity or has low surface tension or a low boiling point. Types of Weighing Weighing for quantitative analysis: The initial step for many quantitative analyses is to accurately weigh a specified amount of a sample. Section 6.50.20 in the General Notices stipulates that solutions for quantitative measures must be prepared using accurately weighed analytes: i.e., analysts must follow <41>. Errors introduced during the weighing of a sample can affect the accuracy of all subsequent analytical measurements. Addition weighing: Addition weighings typically are used for solid samples or liquid samples for which volatility is not an issue. The receiver is placed on the balance. After the balance display stabilizes, the analyst should tare the balance; add the desired amount of material to the receiver; allow the balance display to stabilize; record the weight; and quantitatively transfer the material to an appropriate vessel or, if it cannot be guaranteed that the entire amount has been transferred, weigh the receiver again and note the weight difference. Dispense weighing: Dispense weighing typically is used for weighing emulsions or viscous liquids such as topical ointments. In these situations it is not practical to weigh the material into a typical receiver. Accordingly, the analyst should tare the balance; place the sample on the balance in a suitable container (e.g., a bottle, tube, transfer pipette, or syringe) that has been wiped clean on the outside; record the weight after the balance display stabilizes; transfer the desired amount of sample to an appropriate receiving vessel, such as a volumetric flask; and place the pipette or syringe back onto the balance. The difference in the two weighings is equal to the weight of the transferred specimen. Gravimetric dosing: Gravimetric dosing typically is used for sample and standard preparations or capsule filling. For such weighing the analyst places the volumetric flask, vial, or capsule shell on the balance; tares the balance after the balance display stabilizes; adds the solid or liquid components into the receiver by means of dosing units; and records the respective weights. Problem Samples Electrically charged samples and receivers: Dry, finely divided powders may be charged with static electricity that can make the powder either attracted to or repelled by the receiver or the balance, causing inaccurate weight measurements and specimen loss during transfer. A drift in the balance readings should alert the operator to the possibility that the material has a static charge. Commercially available balances with a built-in antistatic device can be used to remedy the problem. Such devices may use piezoelectric components or a very small amount of a radioactive element (typically polonium) to generate a stream of ions that dissipate the static charge when ed over the powder being weighed. Antistatic weigh boats, antistatic guns, and antistatic screens also are commercially available. The static charge depends also on the relative humidity of the laboratory, which in turn depends on atmospheric conditions. Under certain conditions, static charge is caused by the type of clothing worn by the operator and this charge can cause large errors in the weighing. Borosilicate glassware and plastic receivers have a well-known propensity for picking Chapter 22b
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Reference USP XXVIII Article 1251 « Weighing on an Analytical Balances » revision draft up static charge, especially at low relative humidity. The gloves used to protect the operator also may increase the potential for a static charge problem. Placing the container in a metal holder may help to shield the static charge, and antistatic gloves also can help to alleviate the problem. Volatile samples: When weighing a liquid that has a low boiling point, analysts must receive the specimen in a vessel with a gas-tight enclosure of small diameter. The analyst then tares the vessel and enclosure, adds the desired amount of sample, and replaces the enclosure. After the balance display stabilizes, the analyst records the specimen weight. Warm or cool samples: Samples that are warm or cool should be equilibrated in the laboratory, or the weight readings may be erroneous. With regard to warm samples, the apparent weight is smaller than the true weight because of heat convection. For example, a flask that is warmer than ambient air warms up this air, which then flows upward along the flask and reduces the apparent weight of the contents by viscous friction. Hygroscopic samples: Hygroscopic materials readily absorb moisture from the atmosphere and steadily gain weight if left exposed. Therefore, hygroscopic samples must be either weighed promptly or placed in a vessel with a gas-tight enclosure. For a gas-tight vessel, analysts should tare the vessel and enclosure, add the desired amount of sample, and replace the enclosure. After the balance display stabilizes, the analyst can record the specimen weight. Aseptic or biohazardous samples: The weighing of sterile or biohazardous samples should take place within the confines of a clean bench, biosafety cabinet, isolator, or similar containment device. Air flow within the hood potentially can cause balance instability, so after a balance has been installed under a hood, analysts should perform a rigorous qualification study with suitable weight artifacts (see <41>) in order to determine the acceptability of the balance performance in this environment. Weighing corrosive materials: Many chemicals, such as salts, are corrosive, and materials of this nature should not be spilled on the balance pan or inside the balance housing. Extra care is essential when materials of this nature are weighed. Analysts should consider the use of sealed containers such as weighing bottles or syringes. In the event of a spill, requalification of balance may be necessary, depending on the nature of the spill. Safety Considerations When Weighing During a weighing, the analyst may be exposed to high concentrations of a pure substance. The analyst must carefully consider this possibility at all times and should be familiar with the precautions described in the substance′ s Material Safety Data Sheet before weighing it. Hazardous materials should be handled in an enclosure that has appropriate air filtration. Many toxic – and possibly allergenic – substances present as liquids or finely divided particles. When weighing these substances, analysts should use a mask that covers the nose and mouth to prevent any inhalation of the substance, and they should use gloves to prevent any with the skin. [NOTE – The use of gloves is good practice for handling any chemical. If it is necessary to handle the container being weighed, the analyst should wear gloves not only for self-protection but also to prevent moisture and oils from being deposited on the weighed container.]
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Chapter 22b
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