Pravastatin Sodium Tablets
» Pravastatin Sodium contains not less than 90.0 percent and not more than 110.0 percent of the labeled amount of pravastatin sodium (C23H35NaO7).
Packaging and storage—
Preserve in tight containers. Protect from moisture and light. Store at controlled room temperature.
USP Reference standards 
11
—
11—
USP Pravastatin Related Compound A RS 
3-
-Hydroxyisocompactinor sodium (3R,5R)-3,5-dihydroxy-7-[(1S,2S,3S,8S,8aR)-3-hydroxy-2-methyl-8-[[(2S)-2-methylbutanoyl]oxy]-1,2,3,7,8,8a-hexahydronaphthalen-1-yl]heptanoate.
C23H35NaO7 446.51
') + '&img=../../images/v35300/c11rs2170.gif',600,500);)
3-
-Hydroxyisocompactinor sodium (3R,5R)-3,5-dihydroxy-7-[(1S,2S,3S,8S,8aR)-3-hydroxy-2-methyl-8-[[(2S)-2-methylbutanoyl]oxy]-1,2,3,7,8,8a-hexahydronaphthalen-1-yl]heptanoate.
C23H35NaO7 446.51
USP Pravastatin Related Compound B RS
6¢-Epi-pravastatinor sodium (3R,5R)-3,5-dihydroxy-7-[(1S,2S,6R,8S,8aR)-6-hydroxy-2-methyl-8-[[(2S)-2-methylbutanoyl]oxy]-1,2,6,7,8,8a-hexahydronaphthalen-1-yl]heptanoate.
C23H35NaO7 446.51
') + '&img=../../images/v35300/c11rs2171.gif',600,500);)
6¢-Epi-pravastatinor sodium (3R,5R)-3,5-dihydroxy-7-[(1S,2S,6R,8S,8aR)-6-hydroxy-2-methyl-8-[[(2S)-2-methylbutanoyl]oxy]-1,2,6,7,8,8a-hexahydronaphthalen-1-yl]heptanoate.
C23H35NaO7 446.51
USP Pravastatin Sodium RS
') + '&img=../../images/v35300/cas-81131-70-6.gif',600,500);)
USP Pravastatin 1,1,3,3-Tetramethylbutylamine RS
Identification—
A:
The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.
B:
Ultraviolet Absorption 197U—Finely powder a number of Tablets, and extract with water a portion equivalent to about 10 mg of pravastatin sodium. The UV absorption spectrum of a solution of pravastatin sodium in water containing about 10 µg per mL exhibits maxima at the same wavelength as that of a similar solution of USP Pravastatin Sodium RS, concomitantly measured between 220 and 340 nm.
197U—Finely powder a number of Tablets, and extract with water a portion equivalent to about 10 mg of pravastatin sodium. The UV absorption spectrum of a solution of pravastatin sodium in water containing about 10 µg per mL exhibits maxima at the same wavelength as that of a similar solution of USP Pravastatin Sodium RS, concomitantly measured between 220 and 340 nm.
Dissolution 711—
711—
Medium:
water; 900 mL.
Apparatus 2:
50 rpm.
Time:
30 minutes.
Procedure—
Determine the amount of C23H35NaO7 dissolved by employing UV absorption at the wavelength of maximum absorbance at about 238 nm on filtered portions of the solution under test, suitably diluted with Medium, if necessary, in comparison with a Standard solution having a known concentration of USP Pravastatin 1,1,3,3-Tetramethylbutylamine RS in the same Medium. [note—To express the concentration of the Standard solution as pravastatin sodium, use the conversion factor of (446.51/553.78), in which 446.51 and 553.78 are the molecular weights of pravastatin sodium and pravastatin 1,1,3,3-tetramethylbutylamine, respectively. ]
Tolerances—
Not less than 80% (Q) of the labeled amount of C23H35NaO7 is dissolved in 30 minutes.
Uniformity of dosage units 905:
meet the requirements.
905:
meet the requirements.
Related compounds—
[note—Maintain the Test solution at 15
until injected into the chromatograph. Without refrigeration, the Test solution should be prepared fresh. ]
until injected into the chromatograph. Without refrigeration, the Test solution should be prepared fresh. ]
Diluent—
Prepare a mixture of methanol and water (1:1).
Buffer pH 7.0—
Prepare a 0.08 M phosphoric acid solution, adjust with triethylamine to a pH of 7.0, and mix.
Solution A—
Prepare a filtered and degassed mixture of water, Buffer pH 7.0, and acetonitrile (52:30:18).
Solution B—
Prepare a filtered and degassed mixture of acetonitrile, Buffer pH 7.0, and water (60:30:10).
Mobile phase—
Use variable mixtures of Solution A and Solution B as directed for Chromatographic system. Make adjustments if necessary (see System Suitability under Chromatography 621).
621).
Standard solution—
Dissolve an accurately weighed quantity of USP Pravastatin 1,1,3,3-Tetramethylbutylamine RS in Diluent, and dilute quantitatively, and stepwise if necessary, with Diluent to obtain a solution having a known concentration of about 1.25 µg of pravastatin 1,1,3,3-tetramethylbutylamine per mL.
System suitability solution—
Dissolve accurately weighed quantities of USP Pravastatin 1,1,3,3-Tetramethylbutylamine RS and USP Pravastatin Related Compound A RS in Diluent to obtain a solution containing about 0.6 mg of USP Pravastatin 1,1,3,3-tetramethylbutylamine RS and 0.001 mg of USP Pravastatin Related Compound A RS per mL. [note—USP Pravastatin Related Compound A RS is a sodium salt of 3-hydroxyisocompactin acid. ]
-hydroxyisocompactin acid. ]
Test solution—
Weigh and finely powder not fewer than 20 Tablets. Transfer an accurately weighed portion of the powder, equivalent to about 50 mg of pravastatin sodium, to a 100-mL volumetric flask. Add 60 mL of the Diluent, sonicate for 15–20 minutes, dilute with Diluent to volume, and mix. Pass through a 0.45-µm nylon filter.
Chromatographic system (see Chromatography 621—
The liquid chromatograph is equipped with a 238-nm detector and a 4.6-mm × 7.5-cm column that contains 3.5-µm packing L1. Alternatively, a 4.0-mm × 10-cm column that contains 3-µm packing L1 can be used. The flow rate is about 1 mL per minute. The chromatograph is programmed as follows.
Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the relative retention times are about 1.0 for pravastatin and 1.1 for pravastatin related compound A; and the resolution, R, between pravastatin and pravastatin related compound A is not less than 2.0. Chromatograph the Standard solution, and record the peak responses as directed for Procedure: the relative standard deviation for replicate injections is not more than 10.0%.
621—
The liquid chromatograph is equipped with a 238-nm detector and a 4.6-mm × 7.5-cm column that contains 3.5-µm packing L1. Alternatively, a 4.0-mm × 10-cm column that contains 3-µm packing L1 can be used. The flow rate is about 1 mL per minute. The chromatograph is programmed as follows.
| Time (minutes) |
Solution A
( %) |
Solution B
(%) |
 Elution |
|---|---|---|---|
| 0–3.0 | 100 | 0 | isocratic |
| 3.0–26.5 | 100®0 | 0®100 | linear gradient |
| 26.5–26.6 | 0®100 | 100®0 | linear gradient |
| 26.6–30.0 | 100 | 0 | re-equilibration |
Procedure—
Separately inject equal volumes (about 10 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, identify the impurities listed in Table 1, and measure the peak responses.
Calculate the percentage of each impurity in the portion of Tablets taken by the formula:
Table 1
| Name | Relative Retention Time |
Limit (%) |
|---|---|---|
| Oxidation impurity1 | 0.61 | 1 |
| 6¢-Epipravastatin2 | 0.92 | 0.3 |
| Pravastatin sodium | 1.0 | — |
| Pravastatin lactone | 1.8 | 2 |
| Any other individual impurity | — | 0.2 |
| Total impurities | — | 3 |
|
1
Sodium (3R,5R)-3,5-dihydroxy-7-((1S,2S)-6-hydroxy-2-methyl-1,2-dihydronaphthalen-1-yl)heptanoate.
|
||
|
2
USP Pravastatin Related Compound B RS.
|
||
100×(446.51/553.78)(CS /CT)(ri / rS)
in which 446.51 and 553.78 are the molecular weights of pravastatin sodium and pravastatin 1,1,3,3-tetramethylbutylamine, respectively; CS is the concentration, in mg per mL, of pravastatin 1,1,3,3-tetramethylbutylamine in the Standard solution; CT is the nominal concentration, in mg per mL, of pravastatin sodium in the Test solution; ri is the peak response for each impurity obtained from the Test solution; and rS is the pravastatin peak response obtained from the Standard solution. The reporting level for impurities is 0.1%.
Assay—
[note—The Standard preparation, Assay stock preparation, and Assay preparation can be stored for up to 7 days at room temperature. ]
Mobile phase—
Prepare a filtered and degassed mixture of methanol, water, glacial acetic acid, and triethylamine (500:500:1:1). Make adjustments if necessary (see System Suitability under Chromatography 621).
621).
Diluent 1—
Transfer 16.4 g of anhydrous sodium acetate into a 2000-mL volumetric flask. Add 1600 mL of water, adjust with glacial acetic acid to a pH of 5.6, dilute with water to volume, and mix.
Diluent 2—
Prepare a mixture of Diluent 1 and methanol (80:20).
Standard preparation—
Transfer an accurately weighed quantity of USP Pravastatin 1,1,3,3-Tetramethylbutylamine RS to a suitable volumetric flask, and dissolve in Diluent 1 using sonication to obtain a solution having a known concentration of about 0.6 mg of pravastatin 1,1,3,3-tetramethylbutylamine per mL. Dilute 5.0 mL of this solution with Diluent 2 to 25.0 mL, and mix.
Assay stock preparation—
Transfer not fewer than 5 Tablets to a suitable volumetric flask with at least a (NL×2)-mL capacity, N being the number of Tablets transferred, and L being the label claim per Tablet, filled to at least 80% capacity with Diluent 1. [note—It is necessary to fill the flask to 80% capacity to maintain the correct pH throughout the preparation. ] Shake for at least 1 hour, and sonicate for at least 15 minutes with periodic shaking of the flask by hand, until the Tablets have completely disintegrated. Allow to cool, and dilute with Diluent 1 to volume. Centrifuge a portion of the solution for 15 minutes at 2000 rpm, or filter.
Assay preparation—
Dilute approximately 5 mL of the Assay stock preparation with Diluent 2 to obtain a solution having an expected concentration of about 0.1 mg per mL, based on the label claim.
Resolution solution—
Transfer about 2 mg of USP Pravastatin Related Compound B RS to a 10-mL volumetric flask. Dissolve in and dilute with methanol to volume. Transfer 0.1 mL of this solution and 1.0 mL of the Standard preparation to a small tube, and mix. [note—Pravastatin related compound B is the 6¢-epipravastatin sodium. ]
Chromatographic system (see Chromatography 621)—
The liquid chromatograph is equipped with a 238-nm detector and a 4.6-mm × 5-cm column than contains endcapped packing L1. Alternatively, a 3.9-mm × 7.5-cm column containing endcapped packing L1 can be used. The flow rate is about 1.0 mL per minute. Chromatograph the Resolution solution, and record the peak responses as directed for Procedure: the relative retention times are about 0.7 for pravastatin related compound B and 1.0 for pravastatin; the resolution, R, between the pravastatin related compound B and the pravastatin peaks is not less than 3.0. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the relative standard deviation for replicate injections is not more than 2.0%.
621)—
The liquid chromatograph is equipped with a 238-nm detector and a 4.6-mm × 5-cm column than contains endcapped packing L1. Alternatively, a 3.9-mm × 7.5-cm column containing endcapped packing L1 can be used. The flow rate is about 1.0 mL per minute. Chromatograph the Resolution solution, and record the peak responses as directed for Procedure: the relative retention times are about 0.7 for pravastatin related compound B and 1.0 for pravastatin; the resolution, R, between the pravastatin related compound B and the pravastatin peaks is not less than 3.0. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the relative standard deviation for replicate injections is not more than 2.0%.
Procedure—
Separately inject equal volumes (about 20 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the peak response for pravastatin. Calculate the percentage of pravastatin sodium (C23H35NaO7) in the portion of Tablets taken by the formula:
100(446.51/553.78)(CVD/NL)(rU / rS)
in which 100 is the conversion factor to percentage; 446.51 and 553.78 are the molecular weights of pravastatin sodium and pravastatin 1,1,3,3-tetramethylbutylamine, respectively; C is the concentration, in mg per mL, of pravastatin 1,1,3,3-tetramethylbutylamine in the Standard preparation; V is the volume, in mL, of the Assay stock preparation; D is the dilution factor of the Assay preparation; N is the number of Tablets taken to prepare the Assay stock preparation; L is the label claim, in mg of pravastatin sodium per Tablet; and rU and rS are the pravastatin peak responses obtained from the Assay preparation and the Standard preparation, respectively.
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Elena Gonikberg, Ph.D.
Principal Scientific Liaison 1-301-816-8251 |
(SM32010) Monographs - Small Molecules 3 |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
|
| 711 |
Margareth R.C. Marques, Ph.D.
Senior Scientific Liaison 1-301-816-8106 |
(GCDF2010) General Chapters - Dosage Forms |
USP35–NF30 Page 4390
Pharmacopeial Forum: Volume No. 34(5) Page 1180