Pravastatin Sodium

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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C₂₃H₃₅NaO₇        446.52

1-Naphthaleneheptanoic acid, 1,2,6,7,8,8a-hexahydro-β,δ,6-trihydroxy-2-methyl-8-(2-methyl-1-oxobutoxy)-, monosodium salt, [1S-

[1α(βS*,δS*),2α,6α,8β(R*),8aα]]-;

Sodium (βR,δR,1S,2S,6S,8S,8aR)-1,2,6,7,8,8a-hexahydro-β,δ,6,8-tetrahydroxy-2-methyl-1-naphthaleneheptanoate, 8-[(2S)-2-methylbutyrate] CAS RN®: 81131-70-6; UNII: 3M8608UQ61.

DEFINITION

Pravastatin Sodium contains NLT 97.5% and NMT 102.0% of pravastatin sodium (C₂₃H₃₅NaO₇), calculated on the anhydrous and solvent-free basis.

1 IDENTIFICATION

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K

B. Identification Tests—General 〈191〉, Chemical Identification Tests, Sodium: Meets the requirements of test A • C. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

2 ASSAY

Procedure

Solution A: 0.08 M phosphoric acid solution. Adjust with a 25% sodium hydroxide solution to a pH of 5.5.

Solution B: Acetonitrile and Solution A (20:80)

Solution C: Acetonitrile

Mobile phase: See Table 1.

Table 1

System suitability solution: 0.25 mg/mL of USP Pravastatin 1,1,3,3-Tetramethylbutylamine RS and 0.001 mg/mL of USP Pravastatin Related Compound A RS in methanol

Standard solution: 0.25 mg/mL of USP Pravastatin 1,1,3,3-Tetramethylbutylamine RS in methanol

Sample solution: 0.2 mg/mL of Pravastatin Sodium in methanol

2.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 238 nm

Column: 4.0-mm × 10-cm; 3-µm packing L1

Flow rate: 1 mL/min

Injection volume: 10 µL

2.2 System suitability

Sample: System suitability solution

[Note—The relative retention times for pravastatin and pravastatin related compound A are about 1.0 and 1.2, respectively.] Suitability requirements

Resolution: NLT 1.2 between pravastatin and pravastatin related compound A

Relative standard deviation: NMT 2.0% for the pravastatin peak

2.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of pravastatin sodium (C₂₃H₃₅NaO₇) in the portion of Pravastatin Sodium taken:

Result = (r_U /r_S ) × (C_S /C_U ) × (M_r1 /M_r2 ) × 100

r_U = peak response of pravastatin from the Sample solution

r_S = peak response of pravastatin from the Standard solution

C_S = concentration of USP Pravastatin 1,1,3,3-Tetramethylbutylamine RS in the Standard solution (mg/mL)

C_U = concentration of Pravastatin Sodium in the Sample solution (mg/mL)

M_r1 = molecular weight of pravastatin sodium, 446.52

M_r2 = molecular weight of pravastatin 1,1,3,3-tetramethylbutylamine, 553.78

Acceptance criteria: 97.5%–102.0% on the anhydrous and solvent-free basis

3 IMPURITIES

Organic Impurities

[Note—The Standard solution and the Sample solution are maintained at 15° until injected into the chromatograph.] Diluent: Methanol and water (50:50)

Solution A: 0.08 M phosphoric acid solution. Adjust with triethylamine to a pH of 7.0.

Solution B: Acetonitrile, Solution A, and water (18:30:52)

Solution C: Acetonitrile, Solution A, and water (60:30:10)

Mobile phase: See Table 2.

Table 2

System suitability solution: 0.6 mg/mL of USP Pravastatin 1,1,3,3-Tetramethylbutylamine RS and 0.001 mg/mL of USP Pravastatin Related Compound A RS in Diluent. [Note—USP Pravastatin Related Compound A RS is a sodium salt of 3α-hydroxyisocompactin acid.] Standard solution: 1.25 µg/mL of USP Pravastatin 1,1,3,3-Tetramethylbutylamine RS in Diluent

Sample solution: 0.5 mg/mL of Pravastatin Sodium in Diluent

3.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 238 nm

Column: 4.6-mm × 7.5-cm; 3.5-µm packing L1.

[Note—Alternatively, a 4.0-mm × 10-cm; 3-µm packing L1 can be used.]

Flow rate: 1 mL/min

Injection volume: 10 µL

3.2 System suitability

Samples: System suitability solution and Standard solution

[Note—The relative retention times for pravastatin and pravastatin related compound A are about 1.0 and 1.1, respectively.] Suitability requirements

Resolution: NLT 2.0 between pravastatin and pravastatin related compound A, System suitability solution

Relative standard deviation: NMT 10.0%, Standard solution

3.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each specified or any unspecified impurity in the portion of Pravastatin Sodium taken:

Result = (r_U /r_S ) × (C_S /C_U ) × (M_r1 /M_r2 ) × 100

r_U = peak response of each impurity from the Sample solution

r_S = peak response of pravastatin from the Standard solution

C_S = concentration of USP Pravastatin 1,1,3,3-Tetramethylbutylamine RS in the Standard solution (mg/mL)

C_U = concentration of Pravastatin Sodium in the Sample solution (mg/mL)

M_r1 = molecular weight of pravastatin sodium, 446.52

M_r2 = molecular weight of pravastatin 1,1,3,3-tetramethylbutylamine, 553.78

Acceptance criteria: See Table 3. The reporting level for impurities is 0.05%.

Table 3

a (3R,5R)-3,5-Dihydroxy-7-[(1S,2S,6S,8S,8aR)-6-hydroxy-2-methyl-8-[[(2S)-2-methylpentanoyl]oxy]-1,2,6,7,8,8a-hexahydronaphthalen-1-yl]heptanoic acid.

4 SPECIFIC TESTS

4.1 Limit of Alcohol (if present)

Standard stock solution 1: Pipet 2 mL of dehydrated alcohol into a 100-mL volumetric flask, and dilute with water to volume. Standard stock solution 2: Pipet 10 mL of Standard stock solution 1 into a 100-mL volumetric flask, and dilute with water to volume. Sample stock solution: Transfer 0.2 g of Pravastatin Sodium to a 20-mL volumetric flask, and dilute with water to volume. Sample solution: Pipet 5 mL of the Sample stock solution into a vial fitted with a septum and a crimp cap, add 1 mL of water, seal the vial, and mix. Heat the sealed vial at 80° for 60 min.

Standard solution: Pipet 1 mL of Standard stock solution 2 into a vial fitted with a septum and a crimp cap, and calculate the amount of alcohol (W_A ) added in grams (the specific gravity of dehydrated alcohol is 0.79 g/mL). Add 5 mL of the Sample solution to the same vial, and seal the vial. Heat the sealed vial at 80° for 60 min.

Blank solution: Pipet 6 mL of water into a vial fitted with a septum and a crimp cap, and seal the vial. Heat the sealed vial at 80° for 60 min.

4.1.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: GC

Detector: Flame ionization

Column: 0.53-mm × 30-m fused silica capillary; coated with a 3-µm lm of stationary phase G43

Temperatures

Transfer line: 85°

Injection port: 140°

Detector: 250°

Column: See Table 4.

Table 4

Carrier gas: Helium

Flow rate: Linear velocity of 35 cm/s

Injection volume: 1 mL

Injection type: Split ratio, 1:5

4.1.2 System suitability

Sample: Blank solution

Suitability requirement: No interfering peaks are observed.

4.1.3 Analysis

Samples: Sample solution and Standard solution

Calculate the percentage of alcohol in the portion of Pravastatin Sodium taken:

Result = [r_U /(r_S − r_U )] × (W_A /W) × D × 100

r_U = peak response of alcohol from the Sample solution

r_S = peak response of alcohol from the Standard solution

W_A = amount of alcohol added (g)

W = weight of Pravastatin Sodium taken to prepare the Sample solution (g)

D = dilution factor for the Sample solution, 4

Acceptance criteria: NMT 3.0%

4.2 Optical Rotation 〈781S〉, Procedures, Specific Rotation

Sample solution: 5 mg/mL in water

Acceptance criteria: +150° to +160° (at 20°), calculated on the anhydrous and solvent-free basis

pH 〈791〉: 7.2–9.0, in a solution (1 in 20)

Water Determination 〈921〉, Method I: NMT 4.0%

5 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers. Store as per labeling instructions. Possible storage conditions could include the following, in the presence of stability data supporting the condition: Store under nitrogen in a cold place. Store at room temperature.

Change to read:

USP Reference Standards 〈11〉

USP Pravastatin 1,1,3,3-Tetramethylbutylamine RS

2,4,4-Trimethylpentan-2-amine (3R,5R)-3,5-dihydroxy-7-[(1S,2S,6S,8S,8aR)-6-hydroxy-2-methyl-8-{[(S)-2-methylbutanoyl]oxy}-1,2,6,7,8,8a hexahydronaphthalen-1-yl]heptanoate.

C₂₃H₃₆O₇ · C₈H₁₉N       553.78

USP Pravastatin Sodium RS

USP Pravastatin Related Compound A RS

Sodium (3R,5R)-3,5-dihydroxy-7-[(1S,2R,3S,8S,8aR)-3-hydroxy-2-methyl-8-[[(2S)-2-methylbutanoyl]oxy]-1,2,3,7,8,8a-hexahydronaphthalen-1- yl]heptanoate.

C₂₃H₃₅NaO₇     446.52 (ERR 1-Jun-2020)