Anhydrous Dibasic Calcium Phosphate Pharmacopeial Discussion Group Sign-Off Document
Legend: + will adopt and implement; - will not stipulate. Nonharmonized attributes: Packaging and storage, Heavy metals, Limit of fluoride, Iron Specific local attributes: Identification C (EP), Lead (USP), Description (JP) CaHPO4136.06 Phosphoric acid, calcium salt (1:1); Calcium phosphate (1:1) [7757-93-9]. DEFINITION Anhydrous Dibasic Calcium Phosphate contains NLT 98.0% and NMT 103.0% of anhydrous dibasic calcium phosphate (CaHPO4). IDENTIFICATION • A. Sample: 0.1 g of Anhydrous Dibasic Calcium Phosphate Analysis: Dissolve the Sample by warming in 10 mL of 2 N hydrochloric acid. Add 2.5 mL of ammonia TS dropwise, with shaking, and then add 5 mL of ammonium oxalate TS. Acceptance criteria: A white precipitate is formed. • B. Sample: 0.1 g of Anhydrous Dibasic Calcium Phosphate Analysis: Dissolve the Sample in 5 mL of diluted nitric acid. Warm the solution to 70, and add 2 mL of 10% ammonium molybdate solution (freshly prepared). Acceptance criteria: A yellow precipitate of ammonium phosphomolybdate is formed. ASSAY • Procedure Buffer: Dissolve 53.5 g of ammonium chloride with sufficient water in a 1000-mL volumetric flask. Add 570 mL of ammonia water, stronger, and dilute with water to volume. The pH of this solution is 10.7. Sample solution: Transfer 400 mg of Anhydrous Dibasic Calcium Phosphate to a 200-mL volumetric flask. Dissolve in 12 mL of diluted hydrochloric acid with the aid of gentle heat, if necessary, and dilute with water to volume. Blank: 20 mL of water containing 1.2 mL of diluted hydrochloric acid Titrimetric system (See Titrimetry 541.) Mode: Residual titration Titrant: 0.02 M edetate disodium VS Back-titrant: 0.02 M zinc sulfate VS Endpoint detection: Visual Analysis: To 20.0 mL of the Sample solution add 25.0 mL of Titrant, 50 mL of water, and 5 mL of Buffer. Add 25 mg of eriochrome black Tsodium chloride indicator. Titrate the excess Titrant with the Back-titrant. Perform a Blank determination in the same manner. Calculate the percentage of anhydrous dibasic calcium phosphate (CaHPO4) in the sample taken: Result = {[(VB VS) × M × F]/W} × 100
Acceptance criteria: 98.0%103.0% IMPURITIES • Carbonate Sample: 1.0 g of Anhydrous Dibasic Calcium Phosphate Analysis: Mix the Sample with 5 mL of carbon dioxide-free water, and immediately add 2 mL of hydrochloric acid. Acceptance criteria: No effervescence occurs. • Chloride and Sulfate, Chloride 221 Standard: 0.70 mL of 0.010 N hydrochloric acid Sample: 0.2 g of Anhydrous Dibasic Calcium Phosphate Analysis: To the Sample add 20 mL of water and 13 mL of diluted nitric acid, and warm gently, if necessary, to completely dissolve. Dilute with water to 100 mL, and filter if necessary. To 50 mL of the filtrate add 1 mL of silver nitrate TS. Accceptance criteria: The turbidity of the Sample does not exceed that of the Standard (NMT 0.25%). • Chloride and Sulfate, Sulfate 221 Standard: 1.0 mL of 0.010 N sulfuric acid Sample: 0.5 g of Anhydrous Dibasic Calcium Phosphate Analysis: To the Sample add 5 mL of water and 5 mL of diluted hydrochloric acid, and warm gently, if necessary, to completely dissolve. Dilute with water to 100 mL, and filter if necessary. To 20 mL of the filtrate add 1 mL of diluted hydrochloric acid, and dilute with water to 50 mL. Add 1 mL of barium chloride TS. Accceptance criteria: The turbidity of the Sample does not exceed that of the Standard (NMT 0.5%). • Arsenic, Method I 211 Test preparation: 1.0 g in 25 mL of 3 N hydrochloric acid, diluted with water to 55 mL. Omit the addition of 20 mL of 7 N sulfuric acid specified in Procedure. Acceptance criteria: NMT 3 µg/g • Barium Sample: 0.5 g Anhydrous Dibasic Calcium Phosphate Analysis: Heat the Sample to boiling with 10 mL of water, and add 1 mL of hydrochloric acid dropwise, stirring after each addition. Allow to cool, and filter if necessary. To the filtrate add 2 mL of potassium sulfate TS. Acceptance criteria: No turbidity is produced within 10 min. • Heavy Metals, Method I 231 Test preparation: Warm 1.3 g with 3 mL of 3 N hydrochloric acid to completely dissolve. Cool, dilute with water to 50 mL, and filter. Acceptance criteria: NMT 30 ppm • Limit of Acid-Insoluble Substances Sample solution: Dissolve 5.0 g in a mixture of 40 mL of water and 10 mL of hydrochloric acid by boiling gently for 5 min. Analysis: After cooling, collect the insoluble substance on ashless filter paper, and wash with water until the last washing does not give a reaction for chloride (no turbidity results from the addition of silver nitrate TS). Ignite to completely incinerate the residue and the ashless filter paper at 600 ± 50. Acceptance criteria: The weight of the residue does not exceed 10 mg (NMT 0.2%). • Limit of Fluoride [NotePrepare and store all solutions in plastic containers. ] Buffer solution: 294 mg/mL of sodium citrate dihydrate in water Standard stock solution: 1.1052 mg/mL of USP Sodium Fluoride RS in water Standard solution: Transfer 20.0 mL of Standard stock solution to a 100-mL volumetric flask containing 50.0 mL of Buffer solution, dilute with water to volume, and mix. Each mL of this solution contains 100 µg of fluoride ion. Sample solution: Transfer 2.0 g of Anhydrous Dibasic Calcium Phosphate to a beaker containing a plastic-coated stirring bar. Add 20 mL of water and 2.0 mL of hydrochloric acid, and stir until dissolved. Add 50.0 mL of Buffer solution and sufficient water to make 100 mL. Electrode system: Use a fluoride-specific ion-indicating electrode and a silversilver chloride reference electrode connected to a pH meter capable of measuring potentials with a minimum reproducibility of ±0.2 mV (see pH 791). Analysis Samples: Standard solution and Sample solution Standard response line: Transfer 50.0 mL of Buffer solution and 2.0 mL of hydrochloric acid to a beaker, and add water to make 100 mL. Add a plastic-coated stirring bar, insert the electrodes into the solution, stir for 15 min, and read the potential in mV. Continue stirring, and at 5-min intervals add 100, 100, 300, and 500 µL of Standard solution, reading the potential 5 min after each addition. Plot the logarithms of the cumulative fluoride ion concentrations (0.1, 0.2, 0.5, and 1.0 µg/mL) versus potential in mV. Rinse and dry the electrodes, insert them into the Sample solution, stir for 5 min, and read the potential in mV. From the measured potential and the Standard response line determine the concentration, C (in µg/mL), of fluoride ion in the Sample solution. Calculate the content of fluoride (ppm) in the portion of Anhydrous Dibasic Calcium Phosphate taken: Result = (V × C)/W
Acceptance criteria: NMT 50 ppm SPECIFIC TESTS • Loss on Ignition 733 Sample: 1 g of Anhydrous Dibasic Calcium Phosphate Analysis: Ignite the Sample at 800825 to constant weight. Acceptance criteria: 6.6%8.5% ADDITIONAL REQUIREMENTS • Packaging and Storage: Preserve in well-closed containers. No storage requirements specified. • USP Reference Standards 11 USP Sodium Fluoride RS Auxiliary Information Please check for your question in the FAQs before contacting USP.
USP35NF30 Page 2464 Pharmacopeial Forum: Volume No. 32(4) Page 1332 |