Pravastatin Tablets

General Notices

Action and use

HMG Co-A reductase inhibitor; lipid-regulating drug.

Definition

Pravastatin Tablets contain Pravastatin Sodium.

The tablets comply with the requirements stated under Tablets and with the following requirements.

Content of pravastatin sodium, C₂₃H₃₅NaO₇

92.5 to 107.5% of the stated amount.

Identification

A. Shake a quantity of the powdered tablets containing 10 mg of Pravastatin Sodium with 80 mL of water for 10 minutes, dilute to 100 mL with water, filter and dilute 1 mL to 10 mL with water. The light absorption of the resulting solution, Appendix II B, in the range 220 to 350 nm, exhibits a maximum only at 238 nm.

B. In the Assay, the chromatogram obtained with solution (1) shows a peak with the same retention time as the principal peak in the chromatogram obtained with solution (2).

TESTS

Related substances

Carry out the method for liquid chromatography, Appendix III D, using the following solutions. Dissolve 4.10 g of anhydrous sodium acetate in 400 mL of water, adjust the pH to 5.6 with glacial acetic acid and add sufficient water to produce 500 mL (solution A). Mix 20 volumes of methanol with 80 volumes of solution A (solution B).

(1) Add 20 mL of solution A to a quantity of the powdered tablets containing 10 mg of Pravastatin Sodium, mix using a vortex mixer and then with the aid of ultrasound for 15 minutes. Centrifuge and dilute 1 volume of the clear supernatant liquid to 5 volumes with solution B.

(2) Dilute 1 volume of solution (1) to 100 volumes with solution B.

(3) Dilute 1 volume of solution (2) to 5 volumes with solution B.

(4) Dilute 1 volume of solution (3) to 4 volumes with solution B

(5) Dissolve 2 mg of pravastatin impurity A BPCRS in the minimum volume of methanol and dilute to 20 mL with solution (1).

chromatographic conditions

(a) Use a stainless steel column (15 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5µm) (Ultrasphere ODS is suitable).

(b) Use isocratic elution and the mobile phase described below.

(d) Use a column temperature of 25°.

(e) Use a detection wavelength of 238 nm.

(f) Inject 20 µL of each solution.

mobile phase

1 volume of glacial acetic acid, 1 volume of triethylamine, 450 volumes of methanol and 550 volumes of water.

system suitability

The test is not valid unless, in the chromatogram obtained with solution (5), the resolution factor between the peaks corresponding to pravastatin impurity A and pravastatin is at least 7.0.

limits

In the chromatogram obtained with solution (1):

the area of any secondary peak is not greater than twice the area of the principal peak in the chromatogram obtained with solution (2) (2%);

not more than one secondary peak has an area greater than the area of the principal peak in the chromatogram obtained with solution (2) (1%);

not more than one other secondary peak has an area greater than the area of the principal peak in the chromatogram obtained with solution (3) (0.2%);

the sum of the areas of all secondary peaks is not greater than three times the area of the principal peak in the chromatogram obtained with solution (2) (3%).

Disregard any peak with an area less than the area of the principal peak in the chromatogram obtained with solution (4) (0.05%).

Assay

Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions. Dissolve 4.10 g of anhydrous sodium acetate in 400 mL of water, adjust the pH to 5.6 with glacial acetic acid and add sufficient water to produce 500 mL (solution A). Mix 20 volumes of methanol with 80 volumes of solution A (solution B).

(2) Dissolve 12.4 mg of pravastatin 1,1,3,3,-tetramethylbutylamine BPCRS in 20 mL of solution A and dilute 1 volume to 5 volumes with solution B.

(3) Dissolve 2 mg of pravastatin impurity A BPCRS in the minimum volume of methanol and dilute to 20 mL with solution (1).

chromatographic conditions

The chromatographic conditions described under Related substances may be used.

system suitability

The test is not valid unless, in the chromatogram obtained with solution (3), the resolution factor between the peaks corresponding to pravastatin impurity A and pravastatin is at least 7.0.

determination of content

Calculate the content of C₂₃H₃₅NaO₇ in the tablets using the declared content of C₂₃H₃₆O₇ in pravastatin 1,1,3,3,-tetramethylbutylamine BPCRS. Each mg of C₂₃H₃₆O₇ is equivalent to 1.052 mg of C₂₃H₃₅NaO₇.

Storage

Pravastatin Tablets should be protected from light and moisture.

IMPURITIES

The impurities limited by the requirements of this monograph include those listed under Pravastatin Sodium.