1 GENERAL TESTS, PROCESSES . AND APPARATUS . GENERAL Tests, PROCESSES and APPARATUS includes common netic resonance (NMR) spectroscopy are performed as di- methods for tests, useful test methods for quality recognition rected in the corresponding items under the Crude Drugs of drugs and other articles related to them. Unless otherwise Test. specified, acid-neutralizing capacity determination of gastro- The number of each test method is a category number intestinal medicines, alcohol number determination, amino given individually. The number in blackets (< >) appeared acid analysis of proteins, ammonium determination, arsenic in monograph indicates the number corresponding to the determination, atomic absorption spectrophotometry, boil- GENERAL test method. ing point determination, chloride determination, conduc- tivity measurement, congealing point determination, deter- mination of bulk and tapped densities, digestion test, disintegration test, dissolution test, distilling range determi- 1.
2 Chemical Methods nation, endpoint determination in titrimetry, flame colora- tion, fluorometry, foreign insoluble matter test for injec- tions, foreign insoluble matter test for ophthalmic liquids Alcohol Number and solutions, gas chromatography, glycosylation analysis of Determination glycoprotein, heavy metal determination, inductively cou- pled plasma-atomic emission spectrometry and inductively Alcohol Number Determination represents the number of coupled plasma-mass spectrometry, infrared spectropho- milliliters of ethanol at 159C obtained from 10 mL of tin- tometry, insoluble particulate matter test for injections, in- cture or other preparations containing ethanol by the follow- soluble particulate matter test for ophthalmic liquids and so- ing procedures. lutions, iron determination, liquid chromatography, loss on 1.
3 Method 1 Distilling method drying determination, loss on ignition determination, mass This is a method to determine the Alcohol Number by spectrometry, melting point determination, methanol deter- reading the number of milliliters of ethanol distillate at 159C. mination, methods for color matching, methods of adhesion obtained from 10 mL of a sample measured at 159C by the testing, microbial assay for antibiotics, mineral oil determi- following procedures. nation, nitrogen determination, nuclear magnetic resonance APPARATUS spectroscopy, optical rotation determination, osmolarity de- Use hard glass APPARATUS as illustrated in Fig. termination, oxygen flask combustion method, particle size Ground glass may be used for the joints. determination, particle size distribution test for prepara- Reagent tions, pH determination, powder particle density determina- Alkaline phenolphthalein solution: To 1 g of phenol- tion, qualitative test, refractive index determination, release phthalein add 7 mL of sodium hydroxide TS and water to test for preparations for cutaneous application, residual sol- make 100 mL.
4 Vents test, residue on ignition determination, specific gravity Procedure and density determination, specific surface area determina- Transfer 10 mL of the sample preparation, accurately tion, sulfate determination, test for bacterial endotoxins, test measured at 15 29C, to the distilling flask A, add 5 mL of for glass containers for injections, test for metal particles in water and boiling chips. Distil ethanol carefully into the ophthalmic ointments, test for microbial limit, test for glass-stoppered, volumetric cylinder D. microbial limit for crude drugs, test for plastic containers, By reference to Table , a suitable volume of distil- test for pyrogen, test for readily carbonizable substances, late (mL) should be collected, according to the content of test for rubber closure for aqueous infusions, test for sterili- ethanol in the sample preparation.
5 Ty, test for total organic carbon, test of extractable volume Prevent bumping during distillation by rendering the sam- for injection, thermal analysis, thin-layer chromatography, ple strongly acidic with phosphoric acid or sulfuric acid, or turbidity measurement, ultravioletvisible spectrophotome- by adding a small amount of paraffin, beeswax or silicone try, uniformity of dosage units (test for content uniformity, resin before starting the distillation. mass variation test), viscosity determination, vitamin A. assay, water determination, and X-ray powder diffraction are performed as directed in the corresponding articles under the GENERAL Tests, PROCESSES and APPARATUS . The tests for Table melting point of fats, congealing point of fatty acids, spe- Ethanol content in Distillate cific gravity, acid value, saponification value, ester value, the sample (volz) to be collected hydroxyl value, unsaponifiable matter and iodine value of (mL).
6 Fats and fatty oils are performed as directed in the corre- more than 80 13. sponding items under Fats and Fatty Oils Test, and sam- 80 70 12. pling, preparation of sample for analysis, microscopic ex- 70 60 11. amination, purity test, loss on drying, total ash, acid-insolu- 60 50 10. ble ash, extract content, essential oil content of crude drugs 50 40 9. and assay of marker compounds for the assay of crude drugs 40 30 8. and extracts of Kampo Formulations utilizing nuclear mag- less than 30 7. The JP Drugs are to be tested according to the provisions given in the pertinent monographs, GENERAL Notices, GENERAL Rules for Crude Drugs, 25. GENERAL Rules for Preparations, and GENERAL Tests for their conformity to the Japanese Pharmacopoeia. (See the GENERAL Notices 5.). 26 Alcohol Number Determination / GENERAL Tests JP XVII.
7 (iii). To the distillate add 4 to 6 g of potassium carbonate and 1. to 2 drops of alkaline phenolphthalein solution, and shake vigorously. If the aqueous layer shows no white turbidity, agitate the distillate with additional potassium carbonate. After allowing to stand in water at 15 29C for 30 minutes, read the volume of the upper reddish ethanol layer in mL, and regard it as the Alcohol Number. If there is no clear boundary surface between these two layers, shake vigorously after addition of a few drops of water, then observe in the same manner. 2. Method 2 Gas chromatography This is a method to determine the alcohol number by de- termining ethanol (C2H5OH) content (volz) from a sample measured at 159C by the following procedures. Reagent Ethanol for alcohol number: Ethanol ( ) with deter- mined ethanol (C2H5OH) content.
8 The relation between specific gravity d 15. 15 of ethanol and content of ethanol (C2H5OH) is volz, volz, and volz. Preparation of sample solution and standard solution Sample solution: Measure accurately a volume of sample at 15 29C equivalent to about 5 mL of ethanol (C2H5OH), and add water to make exactly 50 mL. Measure accurately 25 mL of this solution, add exactly 10 mL of the internal standard solution, and add water to make 100 mL. Standard solution: Measure accurately 5 mL of ethanol for alcohol number at the same temperature as the sample, and add water to make exactly 50 mL. Measure accurately 25 mL of this solution, add exactly 10 mL of the internal standard solution, and add water to make 100 mL. Procedure Place 25 mL each of the sample solution and the standard solution in a 100-mL, narrow-mouthed, cylindrical glass bot- tle sealed tightly with a rubber closure and aluminum band, immerse the bottle up to the neck in water, allowed to stand at room temperature for more than 1 hour in a room with lit- tle change in temperature, shake gently so as not to splash Fig.
9 The solution on the closure, and allow to stand for 30. minutes. Perform the test with 1 mL each of the gas in the bottle with a syringe according to the Gas Chromatography < > under the following conditions, and calculate the When the samples contain the following substances, carry ratios, QT and QS, of the peak height of ethanol to that of out pretreatment as follows before distillation. the internal standard. (i) Glycerin: Add sufficient water to the sample so that the residue in the distilling flask, after distillation, contains QT 5 (mL). Alcohol number . at least 50z of water. QS a volume (mL) of sample (ii) Iodine: Decolorize the sample with zinc powder. (iii) Volatile substances: Preparations containing appre- ethanol (C2H5OH) content (volz) of ethanol for alcohol number ciable proportions of essential oil, chloroform, diethyl ether.
10 Or camphor require treatment as follows. Mix 10 mL of the sample, accurately measured, with 10 mL of saturated so- Internal standard solution A solution of acetonitrile (3 in dium chloride solution in a separator, add 10 mL of petro- 50). leum benzin, and shake. Collect the separated aqueous layer. Operating conditions . The petroleum benzin layer was extracted with two 5 mL Detector: A hydrogen flame-ionization detector. portions of saturated sodium chloride solution. Combine the Column: A glass tube about 3 mm in inside diameter and aqueous layers, and distill. According to the ethanol content about m in length, packed with 150- to 180-mm porous in the sample, collect a volume of distillate 2 to 3 mL more ethylvinylbenzene-divinylbenzene copolymer (mean pore than that shown in the above Table.)