Calcium Citrate Tablets
DEFINITION
Calcium Citrate Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of calcium (Ca).
IDENTIFICATION
•  A. The Sample solution from the test for Strength produces line emissions or absorptions at the characteristic wavelengths for calcium.
•  B. Identification Tests—General, Calcium 191 and Citrate 191
Analysis:  Grind a Tablet to a fine powder in a mortar. Transfer the powder to a centrifuge tube, add 2–5 mL of water, sonicate for 1 min, shake, and centrifuge.
Acceptance criteria:  The supernatant meets the requirements of the tests.
STRENGTH
[Note—A standard stock solution is commercially available at different calcium concentrations. Necessary volumetric adjustment can be made in the Standard solution. Concentrations of the Standard solution and the Sample solution may be modified to fit the linear or working range of the instrument. ]
•  Content of Calcium, Procedure 1
Standard stock solution:  Weigh about 1.001 g of calcium carbonate, previously dried at 300 for 3 h and cooled in a desiccator for 2 h, and dissolve in 25 mL of 1 N hydrochloric acid. Boil to expel carbon dioxide, and dilute with water to 100 mL to obtain a solution having a known concentration of about 4000 µg/mL of calcium.
Standard solution:  To a 200-mL volumetric flask add 100 mL of water and 4 mL of nitric acid, and mix thoroughly. Pipet 25.0 mL of the Standard stock solution into the volumetric flask, and dilute with water to volume to obtain a solution having a known concentration of about 500 µg/mL of calcium.
Sample solution:  Weigh and finely powder NLT 20 Tablets. Transfer a weighed portion of the powdered Tablets, equivalent to about 0.1 g of calcium, to a 50-mL flask. Add 4 mL of nitric acid, and heat the solution to boil gently, during which fuming evolves. Boil the solution for an additional 30 min with constant swirling, during which no fuming should be observed. Cool the solution to room temperature, quantitatively transfer all of the solution to a 200-mL volumetric flask, dilute with water to volume, mix, and filter.
Instrumental conditions 
Mode:  ICP–AES
Analytical wavelength:  317.93 nm. [Note—The operating conditions may be developed and optimized based on the manufacturer's recommendation. A typical setting includes radio frequency (RF) power of about 1300 watts, argon torch flow of about 15 L/min, argon auxiliary flow of about 0.2 L/min, and a nebulizer flow rate of about 0.8 L/min. ]
Analysis:  Determine the emission of the Standard solution, the Sample solution, and a 2% nitric acid solution as the blank at the wavelength indicated above.
Calculate the percentage of the labeled amount of calcium (Ca) in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × 100
rU== peak response of calcium from the Sample solution
rS== peak response of calcium from the Standard solution
CS== concentration of calcium in the Standard solution (µg/mL)
CU== nominal concentration of calcium in the Sample solution (µg/mL)
Acceptance criteria:  90.0%–110.0%
•  Content of Calcium, Procedure 2
Lanthanum chloride solution:  267 mg/mL of lanthanum chloride heptahydrate in 0.125 N hydrochloric acid
Calcium standard solution:  Dissolve 1.001 g of calcium carbonate, previously dried at 300 for 3 h and cooled in a desiccator for 2 h, in 25 mL of 1 N hydrochloric acid. Boil to expel carbon dioxide, and dilute with water to 1000 mL to obtain a concentration of 400 µg/mL of calcium.
Standard stock solution:  100 µg/mL of calcium from Calcium standard solution in 0.125 N hydrochloric acid
Standard solutions:  Into separate 100-mL volumetric flasks pipet 1.0, 1.5, 2.0, 2.5, and 3.0 mL of the Standard stock solution. To each flask add 1.0 mL of Lanthanum chloride solution, and dilute with water to volume to obtain concentrations of 1.0, 1.5, 2.0, 2.5, and 3.0 µg/mL of calcium.
Sample solution:  [Note—Finely powder NLT 20 Tablets. ]
Transfer an equivalent to 5 Tablets from powdered Tablets to a porcelain crucible. Heat the crucible in a muffle furnace maintained at 550 for 6–12 h, and cool. Add 60 mL of hydrochloric acid, and boil gently on a hot plate or steam bath for 30 min, intermittently rinsing the inner surface of the crucible with 6 N hydrochloric acid. Cool, and quantitatively transfer the contents of the crucible to a 100-mL volumetric flask. Rinse the crucible with small portions of 6 N hydrochloric acid, and add the rinsings to the flask. Dilute with water to volume, and filter, discarding the first 5 mL of the filtrate. Dilute this solution quantitatively, with 0.125 N hydrochloric acid to obtain a concentration of 2 µg/mL of calcium, adding 1 mL of Lanthanum chloride solution per 100 mL of the final volume.
Instrumental conditions 
Mode:  Atomic absorption spectrophotometry
Analytical wavelength:  Calcium emission line at 422.7 nm
Lamp:  Calcium hollow-cathode
Flame:  Nitrous oxide–acetylene
Blank:  0.125 N hydrochloric acid containing 1 mL of Lanthanum chloride solution per 100 mL
Analysis 
Samples:  Standard solutions and the Sample solution
Determine the absorbances of the solutions, using the Blank. From a linear regression equation, calculated using the absorbance of the Standard solutions versus concentrations, determine the concentration, C, in µg/mL of calcium in the Sample solution.
Calculate the percentage of the labeled amount of calcium (Ca) in the portion of Tablets taken:
Result = (C/CU) × 100
C== determined concentration of calcium in the Sample solution
CU== nominal concentration of calcium in the Sample solution
Acceptance criteria:  90.0%–110.0%
CONTAMINANTS
•  Microbial Enumeration Tests 2021: The total aerobic microbial count does not exceed 1000 cfu/g. The total combined yeasts and molds count does not exceed 100 cfu/g.
•  Absence of Specified Microorganisms 2022: Meet the requirements of the test for absence of Escherichia coli
PERFORMANCE TESTS
•  Disintegration and Dissolution of Dietary Supplements 2040: Meet the requirements for Disintegration, 15 min
•  Weight Variation of Dietary Supplements 2091: Meet the requirements
ADDITIONAL REQUIREMENTS
•  Packaging and Storage: Preserve in well-closed containers.
•  Labeling: The label states the quantity of calcium in terms of mg/Tablet.
Auxiliary Information— Please check for your question in the FAQs before contacting USP.
Topic/Question Contact Expert Committee
Monograph Natalia Davydova
Scientific Liaison
1-301-816-8328
(DS2010) Monographs - Dietary Supplements
2021 Radhakrishna S Tirumalai, Ph.D.
Principal Scientific Liaison
1-301-816-8339
(GCM2010) General Chapters - Microbiology
2022 Radhakrishna S Tirumalai, Ph.D.
Principal Scientific Liaison
1-301-816-8339
(GCM2010) General Chapters - Microbiology
USP35–NF30 Page 1217
Pharmacopeial Forum: Volume No. 34(2) Page 312