Calcium Acetate Capsules
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This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition
Issued and maintained by the United States Pharmacopeial Convention (USP)
To view the Notice from the Expert Committee that posted in conjunction with this accelerated revision, please click
1 DEFINITION
Calcium Acetate Capsules contain NLT 90.0% and NMT 110.0% of the labeled amount of calcium acetate (C4H6CaO4).
2 IDENTIFICATION
A. The retention time of the calcium peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay. B. Identification Tests—General 〈191〉, Chemical Identification Tests, Acetate
Sample solution: 67 mg/mL of calcium acetate from Capsule contents
Acceptance criteria: Meet the requirements for test B
3 ASSAY
Procedure
Solution A: 0.75 mM dipicolinic acid and 1.7 mM nitric acid in water. [Note—Warm water may be required to dissolve dipicolinic acid.] Mobile phase: Acetone and Solution A (10:90). Pass through a suitable filter of 0.2-µm pore size.
Standard solution: 0.08 mg/mL of USP Calcium Acetate RS in water
Sample stock solution: Nominally 6.7 mg/mL of calcium acetate prepared as follows. Transfer an appropriate portion of the contents of NLT 20 Capsules to a suitable volumetric flask. Add water to about 40% of the nal volume of the flask and sonicate for 20 min with intermittent shaking. Dilute with water to volume. Pass through a suitable filter of 0.45-µm pore size.
Sample solution: Nominally 0.08 mg/mL of calcium acetate in water from the Sample stock solution
Chromatographic system
(See Chromatography 〈621〉, System Suitability.)
Mode: Ion chromatography
Detector: Conductivity
Column: 4.0-mm × 15-cm; 5-µm packing L76
Column temperature: 35°
Flow rate: 0.9 mL/min
Injection volume: 10 µL
Run time: NLT 1.5 times the retention time of the calcium peak
System suitability
Sample: Standard solution
Suitability requirements
Column efficiency: NLT 1000 theoretical plates
Relative standard deviation: NMT 2.0%
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of the labeled amount of calcium acetate (C4H6CaO4) in the portion of Capsules 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 USP Calcium Acetate RS in the Standard solution (mg/mL)
CU = nominal concentration of calcium acetate in the Sample solution (mg/mL)
Acceptance criteria: 90.0%–110.0%
PERFORMANCE TESTS
Change to read:
Dissolution 〈711〉
Test 1
Medium: Water; 900 mL
Apparatus 2: 50 rpm, with sinkers
Time: 10 min
Solution A, Mobile phase, Standard solution, Chromatographic system, and System suitability: Proceed as directed in the Assay. Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size. Dilute with Medium to a concentration similar to the Standard solution, if necessary.
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of the labeled amount of calcium acetate (C4H6CaO4) dissolved:
Result = rU/rS) × CS × V × D × (1/L) × 100
rU = peak response of calcium from the Sample solution
rS = peak response of calcium from the Standard solution
CS = concentration of USP Calcium Acetate RS in the Standard solution (mg/mL)
V = volume of Medium, 900 mL
D = dilution factor of the Sample solution, if needed
L = label claim (mg/Capsule)
Tolerances: NLT 80% (Q) of the labeled amount of calcium acetate (C4H6CaO4) is dissolved.
Test 2: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2.
Medium: 0.1 N hydrochloric acid; 900 mL
Apparatus 1: 100 rpm
Time: 15 min
Blank: 0.2% (v/v) nitric acid
Standard solution A: 4.0 µg/mL of calcium1 in the Blank
Standard solution B: 5.0 µg/mL of calcium1 in the Blank
Standard solution C: 6.0 µg/mL of calcium1 in the Blank
Standard solution D: 7.0 µg/mL of calcium1 in the Blank
Standard solution E: 8.0 µg/mL of calcium1 in the Blank
Sample solution: Pass a portion of the solution under test through a suitable filter of 1.0-µm pore size. Dilute with Blank to a concentration similar to Standard solution C, if necessary.
Instrumental conditions
(See Atomic Absorption Spectroscopy 〈852〉.)
Mode: Atomic absorption spectrometry
Analytical wavelength: 422.8 nm
Lamp: Calcium hollow-cathode
Flame: Air–acetylene oxidizing ame
System suitability
Samples: Blank, Standard solution A, Standard solution B, Standard solution C, Standard solution D, and Standard solution E Suitability requirements
Correlation coefficient: NLT 0.995, from the linear regression in the Analysis
Drift: Within ±2%, Standard solution D. (See Atomic Absorption Spectroscopy 〈852〉, Procedure, Analysis.)
Analysis
Samples: Blank, Standard solution A, Standard solution B, Standard solution C, Standard solution D, Standard solution E, and Sample solution Use the Blank to set the instrument to zero. Concomitantly determine the responses for Standard solution A, Standard solution B, Standard solution C, Standard solution D, and Standard solution E. Construct a linear calibration curve by plotting the absorbance values of Standard solution A, Standard solution B, Standard solution C, Standard solution D, and Standard solution E versus their corresponding concentrations, in μg/mL. From the linear calibration curve, determine the concentration (C), in µg/mL, for calcium in the Sample solution.
Calculate the percentage of the labeled amount of calcium acetate (C4H6CaO4) dissolved:
Result = C × V × F × D × (Mr1/Mr2) × (1/L) × 100
C = concentration of calcium in the Sample solution (µg/mL)
V = volume of Medium, 900 mL
F = conversion factor, 0.001 mg/µg
D = dilution factor of the Sample solution, if needed
Mr1 = molecular weight of calcium acetate, 158.17
Mr2 = molecular weight of calcium, 40.08
L = label claim (mg/Capsule)
Tolerances: NLT 85% (Q) of the labeled amount of calcium acetate (C4H6CaO4) is dissolved.
Test 3: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 3.
Tier 1
Medium 1: Water; 900 mL
Apparatus 2: 100 rpm, with sinkers
Time: 15 min
Tier 2
Medium 2: Simulated gastric uid TS; 900 mL
Apparatus 2: 100 rpm, with sinkers
Time: 15 min
Determine the amount of calcium acetate dissolved using Analytical procedure 1 or Analytical procedure 2 for Tier 1 and Analytical procedure 3 for Tier 2.
Sample stock solution: Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size.
Dissolution procedure: Perform the test using the conditions in Tier 1. In the presence of cross-linking, repeat the test with a new set of
Capsules using the conditions in Tier 2.
Analytical procedure 1
Blank: 0.02 N nitric acid
Standard solution A: 2.4 µg/mL of USP Calcium Acetate RS in the Blank
Standard solution B: 3.2 µg/mL of USP Calcium Acetate RS in the Blank
Standard solution C: 4.0 µg/mL of USP Calcium Acetate RS in the Blank
Standard solution D: 4.8 µg/mL of USP Calcium Acetate RS in the Blank
Standard solution E: 5.6 µg/mL of USP Calcium Acetate RS in the Blank
Sample solution: Nominally 3.7 µg/mL of calcium acetate from Sample stock solution. Dilute with Blank if necessary. Instrumental conditions
(See Atomic Absorption Spectroscopy 〈852〉.)
Mode: Atomic absorption spectrometry
Analytical wavelength: 422.8 nm
Lamp: Calcium hollow-cathode
Flame: Nitrous oxide–acetylene
Replicates: 4
System suitability
Samples: Blank, Standard solution A, Standard solution B, Standard solution C, Standard solution D, Standard solution E, and Sample solution
Suitability requirements
Relative standard deviation: NMT 3.0% in 4 replicate measurements, Standard solution A, Standard solution B, Standard solution C, Standard solution D, Standard solution E, and Sample solution
Correlation coefficient: NLT 0.995, from the linear regression in the Analysis
Drift: Within ±5%, the absorbance value of Standard solution E. (See Atomic Absorption Spectroscopy 〈852〉, Procedure, Analysis.) Analysis
Samples: Blank, Standard solution A, Standard solution B, Standard solution C, Standard solution D, Standard solution E, and Sample solution
Use the Blank to set the instrument to zero. Concomitantly determine the responses for Standard solution A, Standard solution B, Standard solution C, Standard solution D, and Standard solution E. Construct a quadratic calibration curve by plotting the absorbance values of Standard solution A, Standard solution B, Standard solution C, Standard solution D, and Standard solution E versus their corresponding concentrations, in μg/mL. From the quadratic calibration curve, determine the concentration (C), in µg/mL, for calcium acetate in the Sample solution.
Calculate the percentage of the labeled amount of calcium acetate (C4H6CaO4) dissolved:
Result = C × V × F × D × (1/L) × 100
C = concentration of calcium acetate in the Sample solution (µg/mL)
V = volume of Medium 1, 900 mL
F = conversion factor, 0.001 mg/µg
D = dilution factor of the Sample solution, if needed
L = label claim (mg/Capsule)
Analytical procedure 2
Titrimetric system
(See Titrimetry 〈541〉.)
Mode: Complexometric titration
Titrant: 0.005 M edetic acid (EDTA)
Endpoint detection: Photometric at 610 nm
Analysis: To an aliquot of the Sample stock solution equivalent to about 7.4 mg of calcium acetate, add 60 mL of 0.1 N sodium hydroxide and 0.2 g of hydroxy naphthol blue indicator. Titrate with Titrant, determining the endpoint photometrically using a suitable autotitrator. Calculate the percentage of the labeled amount of calcium acetate (C4H6CaO4) dissolved:
Result = VS × M × F × (VM/VA) × (1/L) × 100
VS = volume of Titrant consumed by the aliquot of Sample stock solution (mL)
M = actual molarity of the Titrant (mmol/mL)
F = equivalency factor of calcium acetate, 158.17 mg/mmol
VM = volume of Medium 1, 900 mL
VA = volume of the aliquot taken (mL)
L = label claim (mg/Capsule)
Analytical procedure 3
Blank: Medium 2
Titrimetric system
(See Titrimetry 〈541〉.)
Mode: Complexometric titration
Titrant: 0.005 M edetic acid (EDTA)
Endpoint detection: Visual
Analysis: To an aliquot of the Sample stock solution equivalent to about 7.4 mg of calcium acetate, add 50 mL of water, 10 mL of 0.1 N sodium hydroxide, and 0.2 g of hydroxynaphthol blue indicator. Titrate with Titrant to a blue endpoint while stirring using a magnetic stirring bar. Perform a Blank determination in the same manner.
Calculate the percentage of the labeled amount of calcium acetate (C4H6CaO4) dissolved:
Result = (VS − VB) × M × F × (VM/VA) × (1/L) × 100
VS = volume of Titrant consumed by the aliquot of Sample stock solution (mL)
VB = volume of Titrant consumed by the Blank (mL)
M = actual molarity of the Titrant (mmol/mL)
F = equivalency factor of calcium acetate, 158.17 mg/mmol
VM = volume of Medium 2, 900 mL
VA = volume of the aliquot taken (mL)
L = label claim (mg/Capsule)
Tolerances: NLT 85% (Q) of the labeled amount of calcium acetate (C4H6CaO4) is dissolved.
Test 4: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 4.
Medium: Water; 900 mL, deaerated
Apparatus 2: 50 rpm, with appropriate sinkers, if necessary
Time: 20 min
Solution A: 0.7% (v/v) phosphoric acid in water
Mobile phase: Methanol and Solution A (5:95)
Standard solution: 0.74 mg/mL of USP Calcium Acetate RS in Medium
Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size.
Chromatographic system
(See Chromatography 〈621〉, System Suitability.)
Mode: LC
Detector: UV 202 nm
Column: 4.6-mm × 25-cm; 5-µm packing L1
Flow rate: 1 mL/min
Injection volume: 10 µL
Run time: NLT 2 times the retention time of the acetate peak
System suitability
Sample: Standard solution
Suitability requirements
Tailing factor: NMT 2.0
Relative standard deviation: NMT 2.0%
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of the labeled amount of calcium acetate (C4H6CaO4) dissolved:
Result = (rU/rS) × CS × V × (1/L) × 100
rU = peak response of acetate from the Sample solution
rS = peak response of acetate from the Standard solution
CS = concentration of USP Calcium Acetate RS in the Standard solution (mg/mL)
V = volume of Medium, 900 mL
L = label claim (mg/Capsule)
Tolerances: NLT 85% (Q) of the labeled amount of calcium acetate (C4H6CaO4) is dissolved.
Test 5: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 5.
Medium: 0.1 N hydrochloric acid; 500 mL
Apparatus 2: 50 rpm, with suitable sinkers if necessary
Time: 30 min
Solution A: 0.7 mL/L of phosphoric acid in water
Mobile phase: Methanol and Solution A (5:95)
Standard solution: 0.74 mg/mL of USP Calcium Acetate RS in Medium
Sample solution: Dilute a portion of the solution under test with Medium to a concentration similar to that of the Standard solution. Pass through a suitable filter of 0.45-µm pore size, discarding the first 3 mL of the filtrate.
Chromatographic system
(See Chromatography 〈621〉, System Suitability.)
Mode: LC
Detector: UV 202 nm
Column: 4.6-mm × 25-cm; 5-µm packing L1
Flow rate: 1 mL/min
Injection volume: 10 µL
Run time: NLT 2 times the retention time of acetate
System suitability
Sample: Standard solution
Suitability requirements
Tailing factor: NMT 2.0
Relative standard deviation: NMT 2.0%
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of the labeled amount of calcium acetate (C4H6CaO4) dissolved:
Result = (rU/rS) × CS × V × D x (1/L) × 100
rU = peak response of acetate from the Sample solution
rS = peak response of acetate from the Standard solution
CS = concentration of USP Calcium Acetate RS in the Standard solution (mg/mL)
V = volume of Medium, 500 mL
D = dilution factor of the Sample solution
L = label claim (mg/Capsule)
Tolerances: NLT 80% (Q) of the labeled amount of calcium acetate (C4H6CaO4) is dissolved.
Uniformity of Dosage Units 〈905〉: Meet the requirements
4 ADDITIONAL REQUIREMENTS
Packaging and Storage: Preserve in well-closed containers and store at controlled room temperature.
Labeling: When more than one Dissolution test is given, the labeling states the Dissolution test used only if Test 1 is not used. USP Reference Standards 〈11〉
USP Calcium Acetate RS
1 From commercially available, National Institute of Standards and Technology (NIST)-traceable standard solution for calcium.
