Anhydrous Dibasic Calcium Phosphate
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AttributeJPEPUSP
Definition+++
Identification A+++
Identification B+++
Acid-insoluble substances+++
Chloride+++
Sulfate+++
Carbonate+++
Barium+++
Loss on ignition+++
Assay+++
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 
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 T–sodium 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
VB== Back-titrant volume consumed by the Blank (mL)
VS== Back-titrant volume consumed by the Sample (mL)
M== actual molarity of the Back-titrant (mM/mL)
F== equivalency factor, 136.06 mg/mM
W== Sample weight (mg)
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
[Note—Prepare 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 silver–silver 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
V== Sample solution volume (mL)
C== concentration of fluoride ion, determined from the Standard response line, in the Sample solution (µg/mL)
W== weight of Anhydrous Dibasic Calcium Phosphate taken to prepare the Sample solution (g)
Acceptance criteria: NMT 50 ppm
SPECIFIC TESTS
•  Loss on Ignition 733
Sample: 1 g of Anhydrous Dibasic Calcium Phosphate
Analysis: Ignite the Sample at 800–825 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.
Topic/QuestionContactExpert Committee
MonographHuy T. Dinh, M.S.
Scientific Liaison
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USP35–NF30 Page 2464
Pharmacopeial Forum: Volume No. 32(4) Page 1332