BRIEFING

Atorvastatin Calcium Tablets. Because there is no existing USP monograph for this dosage form, a new monograph, based on validated methods of analyses, is proposed. The HPLC procedures in the Assay and in the test for Organic Impurities are based on analyses performed with the Ultremex C18 brand of L1 column. The typical retention time for atorvastatin is about 9 min.

(SM3: E. Gonikberg, L. Santos, M. Marques.)

Correspondence Number—C97231

Comment deadline: November 30, 2011

Add the following:

Atorvastatin Calcium Tablets

DEFINITION

Atorvastatin Calcium Tablets contain an amount of atorvastatin calcium (C33H34FN2O5)2Ca equivalent to NLT 94.5% and NMT 105.0% of the labeled amount of atorvastatin.

IDENTIFICATION

•  A. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

ASSAY

•  Procedure

Buffer:  0.05 M ammonium citrate buffer pH 4.0 prepared as follows. Dissolve 9.62 g of anhydrous citric acid in 950 mL of water, adjust with ammonium hydroxide to a pH of 4.0, and dilute with water to 1000 mL.

Mobile phase:  Acetonitrile, stabilizer-free tetrahydrofuran, and Buffer (27:20:53)

Diluent:  Dissolve 9.62 g of anhydrous citric acid in 900 mL of water, adjust with ammonium hydroxide to a pH of 7.4, and dilute with water to 1000 mL. Mix 1000 mL of this solution with 1000 mL of acetonitrile.

System suitability solution:  0.1 mg/mL of USP Atorvastatin Calcium RS and 0.01 mg/mL of USP Atorvastatin Related Compound H RS in Diluent. Shake mechanically for 30 min or until dissolved.

Standard solution:  0.1 mg/mL of USP Atorvastatin Calcium RS in Diluent. Shake mechanically for 15 min or until dissolved.

Sample solution:  Transfer 10 Tablets into an appropriate volumetric flask. Add Diluent to about 50% of the final volume of the flask, and shake the mixture mechanically for 15 min or until completely dissolved. Dilute with Diluent to volume. Further dilute the solution with Diluent to obtain a solution containing 0.1 mg/mL of atorvastatin based on the label claim, and pass the solution through a suitable filter.

Chromatographic system 
(See Chromatography 621, System Suitability.)

Mode:  LC

Detector:  UV 244 nm

Column:  4.6-mm × 25-cm; 5-µm packing L1

Flow rate:  1.5 mL/min

Injection size:  20 µL

System suitability 

Samples:  System suitability solution and Standard solution

Suitability requirements 

Resolution:  NLT 5.0 between atorvastatin and atorvastatin related compound H, System suitability solution

Tailing factor:  NMT 1.2 for atorvastatin, System suitability solution

Relative standard deviation:  NMT 1.0%, Standard solution

Analysis 

Samples:  Standard solution and Sample solution

Calculate the percentage of the labeled amount of atorvastatin (C33H35FN2O5) in the portion of Tablets taken:

Result = (rU/rS) × (CS/CU) × (2 × Mr1/Mr2) × 100

Acceptance criteria:  94.5.0%–105.0%

PERFORMANCE TESTS

•  Dissolution 711:

Medium:  pH 6.8, 0.05 M phosphate buffer; 900 mL

Apparatus 2:  75 rpm

Time:  15 min

Diluent:  Acetonitrile and water (50:50)

Standard stock solution:  1.0 mg/mL of USP Atorvastatin Calcium RS in Diluent. Shake mechanically for 10 min or until dissolved.

Standard solution:  Dilute the Standard stock solution with Medium to obtain a final concentration of (L/900) mg/mL, where L is the label claim in mg/Tablet.

Sample solution:  Pass a portion of the solution under test through a suitable filter.

Instrumental conditions 
(See Spectrophotometry and Light-Scattering 851.)

Analytical wavelength:  244 nm

Cell path:  See Table 1.

Table 1

Blank:  Medium

Analysis 

Samples:  Standard solution and Sample solution

Calculate the percentage of the labeled amount of atorvastatin (C33H35FN2O5) dissolved:

(AU/AS) × (CS/L) × (2 × Mr1/Mr2) × V × 100

Tolerances:  NLT 80% (Q) of the labeled amount of atorvastatin (C33H35FN2O5) is dissolved.

•  Uniformity of Dosage Units 905:

Diluent:  Acetonitrile and water (50:50)

Standard solution:  0.1 mg/mL of USP Atorvastatin Calcium RS in Diluent. Shake mechanically for 15 min or until dissolved.

Sample solution:  Place each Tablet into a separate appropriately sized volumetric flask. Add Diluent to about 50% of the final volume of the flask, and shake the mixture mechanically for 15 min or until completely dissolved. Dilute with Diluent to volume. Further dilute the solution with Diluent to obtain a solution containing 0.1 mg/mL of atorvastatin based on the label claim, and pass the solution through a suitable filter.

Instrumental conditions 
(See Spectrophotometry and Light-Scattering 851.)

Mode:  UV

Cell:  0.1 cm

Absorbance:  244 nm

Blank:  Diluent

Analysis 

Samples:  Standard solution and Sample solution

Calculate the percentage of the labeled amount of atorvastatin (C33H35FN2O5) in the Tablet taken:

Result = (AU/AS) × (CS/CU) × (2 × Mr1/Mr2) × 100

Acceptance criteria:  Meets the requirements

IMPURITIES

•  Organic Impurities

Buffer, Mobile phase, Diluent, System suitability solution, Standard solution, and Sample solution:  Proceed as directed in the Assay.

Chromatographic system:  Proceed as directed in the Assay, except record the chromatograms for at least three times the retention time of atorvastatin.

System suitability 

Sample:  System suitability solution

Suitability requirements 

Resolution:  NLT 5.0 between atorvastatin and atorvastatin related compound H

Tailing factor:  NMT 1.2 for the atorvastatin peak and less than 1.5 for the atorvastatin related compound H peak

Relative standard deviation:  NMT 2.0% for atorvastatin related compound H

Analysis 

Sample:  Sample solution

Calculate the percentage of any individual impurity in the portion of Tablets taken:

Result = (rU/rT) × 100

Acceptance criteria:  See Table 2.

Table 2

ADDITIONAL REQUIREMENTS

•  Packaging and Storage: Preserve in tight containers, and store at controlled room temperature.

•  USP Reference Standards 11

USP Atorvastatin Calcium RS

USP Atorvastatin Related Compound H RS (lactone impurity)
5-(4-Fluorophenyl)-1-{2-[(2R,4R)-4-hydroxy-6-oxotetrahydro-2H-pyran-2-yl]ethyl}-2-isopropyl-N,4-diphenyl-1H-pyrrole-3-carboxamide.     C33H33FN2O4       540.62

2S (USP35)

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