6. TESTING PRACTICES AND PROCEDURES
6.10. Safe Laboratory Practices
In performing compendial procedures, safe laboratory practices shall be followed, including precautionary measures, protective equipment, and work practices consistent with the chemicals and procedures used. Before undertaking any procedure described in the compendia, the analyst should be aware of the hazards associated with the chemicals and the techniques and means of protecting against them. These compendia are not designed to describe such hazards or protective measures.
6.20. Automated Procedures
Automated and manual procedures employing the same basic chemistry are considered equivalent.
6.30. Alternative and Harmonized Methods and Procedures
Alternative methods and/or procedures may be used if they provide advantages in terms of accuracy, sensitivity, precision, selectivity, or adaptability to automation or computerized data reduction, or in other special circumstances. Such alternative procedures and methods shall be validated as described in the general chapter Validation of Compendial Procedures 1225 and must be shown to give equivalent or better results. Only those results obtained by the methods and procedures given in the compendium are conclusive.
Alternative procedures should be submitted to USP for evaluation as a potential replacement or addition to the standard (see section 4.10, Monographs).
Certain general chapters contain a statement that the text in question is harmonized with the corresponding text of the European Pharmacopoeia and/or the Japanese Pharmacopoeia and that these texts are interchangeable. Therefore, if a substance or preparation is found to comply with a requirement using an interchangeable method or procedure from one of these pharmacopeias, it should comply with the requirements of the USP. When a difference appears, or in the event of dispute, only the result obtained by the method and/or procedure given in the USP is conclusive.
6.40. Dried, Anhydrous, Ignited, or Solvent-Free Basis
All calculations in the compendia assume an “as-is” basis unless otherwise specified.
Test procedures may be performed on the undried or unignited substance and the results calculated on the dried, anhydrous, or ignited basis, provided a test for Loss on drying, or Water, or Loss on ignition, respectively, is given in the monograph. Where the presence of moisture or other volatile material may interfere with the procedure, previous drying of the substance is specified in the individual monograph and is obligatory.
The term “solvent-free” signifies that the calculation shall be corrected for the presence of known solvents as determined using the methods described in Residual Solvents 467 unless a test for limit of organic solvents is provided in the monograph.
The term “previously dried” without qualification signifies that the substance shall be dried as directed under Loss on Drying 731 or Water Determination 921 (gravimetric determination).
Where drying in vacuum over a desiccant is directed, a vacuum desiccator, a vacuum drying pistol, or other suitable vacuum drying apparatus shall be used.
6.40.10. Ignite To Constant Weight
“Ignite to constant weight” means that ignition shall be continued at 800 ± 25, unless otherwise indicated, until two consecutive weighings, the second of which is taken after an additional period appropriate to the nature and quantity of the residue, do not differ by more than 0.50 mg per g of substance taken.
6.40.20. Dried To Constant Weight
“Dried to constant weight” means that drying shall be continued until two consecutive weighings, the second of which is taken after an additional drying period appropriate to the nature and quantity of the residue, do not differ by more than 0.50 mg per g of substance taken.
6.50. Preparation of Solutions
6.50.10. Filtration
Where a procedure gives direction to “filter” without further qualification, the liquid shall be passed through suitable filter paper or equivalent device until the filtrate is clear. Due to the possibility of filter effects, the initial volumes of a filtrate may be discarded.
6.50.20. Solutions
Unless otherwise specified, all solutions shall be prepared with Purified Water. Solutions for quantitative measures shall be prepared using accurately weighed or accurately measured analytes (see section 8.20, About).
An expression such as “(1 in 10)” means that 1 part by volume of a liquid shall be diluted with, or 1 part by weight of a solid shall be dissolved in, a sufficient quantity of the diluent or solvent to make the volume of the finished solution 10 parts by volume. An expression such as “(20:5:2)” means that the respective numbers of parts, by volume, of the designated liquids shall be mixed, unless otherwise indicated.
6.50.20.1. Adjustments to Solutions
When a specified concentration is called for in a procedure, a solution of other normality or molarity may be used, provided that allowance is made for the difference in concentration and that the change does not increase the error of measurement.
Unless otherwise indicated, analyte concentrations shall be prepared to within ten percent (10%) of the indicated value. In the special case in which a procedure is adapted to the working range of an instrument, solution concentrations may differ from the indicated value by more than ten percent (10%), with appropriate changes in associated calculations. Any changes shall fall within the validated range of the instrument.
When adjustment of pH is indicated with either an acid or base and the concentration is not indicated, appropriate concentrations of that acid or base may be used.
6.50.20.2. Test Solutions
Information on Test Solutions (TS) is provided in the Test Solutions portion of the Reagents, Indicators, and Solutions section of the USP–NF. Use of an alternative Test Solution or a change in the Test Solution used may require validation.
6.50.20.3. Indicator Solutions
Where a procedure specifies the use of an indicator TS, approximately 0.2 mL, or 3 drops, of the solution shall be added unless otherwise directed.
6.60. Units Necessary to Complete a Test
Unless otherwise specified, a sufficient number of units to ensure a suitable analytical result shall be taken.
6.60.10. Tablets
Where the procedure of a Tablet monograph directs to weigh and finely powder not fewer than a given number of Tablets, a counted number of Tablets shall be weighed and reduced to a powder. The portion of the powdered Tablets taken shall be representative of the whole Tablets and shall, in turn, be weighed accurately.
6.60.20. Capsules
Where the procedure of a Capsule monograph gives direction to remove, as completely as possible, the contents of not fewer than a given number of the Capsules, a counted number of Capsules shall be carefully opened and the contents quantitatively removed, combined, mixed, and weighed accurately. The portion of mixed Capsules contents taken shall be representative of the contents of the Capsules and shall, in turn, be weighed accurately.
6.70. Reagents
The proper conduct of the compendial procedures and the reliability of the results depend, in part, upon the quality of the reagents used in the performance of the procedures. Unless otherwise specified, reagents conforming to the specifications set forth in the current edition of Reagent Chemicals published by the American Chemical Society (ACS) shall be used. Where such ACS reagent specifications are not available or where the required purity differs, compendial specifications for reagents of acceptable quality are provided (see the Reagents, Indicators, and Solutions section of the USP–NF). Reagents not covered by any of these specifications should be of a grade suitable to the proper performance of the method of assay or test involved.
Listing of these reagents, including the indicators and solutions employed as reagents, in no way implies that they have therapeutic utility; furthermore, any reference to USP or NF in their labeling shall include also the term “reagent” or “reagent grade.” USP may supply reagents if they otherwise may not be generally commercially available.
6.80. Equipment
Unless otherwise specified, a specification for a definite size or type of container or apparatus in a procedure is given solely as a recommendation. Other dimensions or types may be used if they are suitable for the intended use.
6.80.10. Apparatus for Measurement
Where volumetric flasks or other exact measuring, weighing, or sorting devices are specified, this or other equipment of at least equivalent accuracy shall be employed.
6.80.10.1. Pipet
Where a pipet is specified, a suitable buret may be substituted. Where a “to contain” pipet is specified, a suitable volumetric flask may be substituted.
6.80.10.2. Light Protection
Where low-actinic or light-resistant containers are specified, either containers specially treated to protect contents from light or clear containers that have been rendered opaque by application of a suitable coating or wrapping may be used.
6.80.20. Instrumental Apparatus
An instrument may be substituted for the specified instrument if the substitute uses the same fundamental principles of operation and is of equivalent or greater sensitivity and accuracy. These characteristics shall be qualified as appropriate. Where a particular brand or source of a material, instrument, or piece of equipment, or the name and address of a manufacturer or distributor, is mentioned (ordinarily in a footnote), this identification is furnished solely for informational purposes as a matter of convenience, without implication of approval, endorsement, or certification.
6.80.20.1. Chromatographic Tubes and Columns
The term “diameter” refers to internal diameter (ID).
6.80.20.2. Tubing
The term “diameter” refers to outside diameter (OD).
6.80.20.3. Steam Bath
Where use of a steam bath is directed, use actively flowing steam or another regulated heat source controlled at an equivalent temperature.
6.80.20.4. Water Bath
A water bath requires vigorously boiling water unless otherwise specified.