Fluvastatin 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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C₂₄H₂₅FNNaO₄ 433.45

6-Heptenoic acid, 7-[3-(4-fluorophenyl)-1-(1-methyl ethyl)-1H-indol-2-yl]-3,5-dihydroxy-, monosodium salt, [R*,S*-(E)]-(±)-;

Sodium (±)-(3R*,5S*,6E)-7-[3-(p-fluorophenyl)-1-iso propylindol-2-yl]-3,5-dihydroxy-6-heptenoate CAS RN^®: 93957-55-2; UNII: PYF7O1FV7F.

1 DEFINITION

Fluvastatin Sodium contains NLT 98.0% and NMT 102.0% of fluvastatin sodium (C₂₄H₂₅FNNaO₄), calculated on the anhydrous basis.

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197A or 197K (CN 1-May-2020)

If a difference appears in the IR spectra of the analyte and the Standard, dissolve equal portions of the sample specimen and the USP Reference Standard in equal volumes of methanol. Evaporate the solutions to dryness on a steam bath, protecting the solutions from light, and dry at 105° for 30 min. Repeat the test on the residues.

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.

3 ASSAY

3.1 PROCEDURE

Solution A: Add 20 mL of 25% aqueous tetramethylammonium hydroxide solution to 880 mL of water. Adjust with about 2.3 mL of phosphoric acid to a pH of 7.2 ± 0.2. Add 100 mL of a mixture of methanol and acetonitrile (60:40).

Solution B: Add 20 mL of 25% aqueous tetramethylammonium hydroxide solution and 80 mL of water to 900 mL of a mixture of methanol and acetonitrile (60:40). Adjust with about 2.3 mL of phosphoric acid to a pH of 7.2 ± 0.2.

Mobile phase: See Table 1.

Table 1

System suitability solution: 0.5 mg/mL of fluvastatin sodium from USP Fluvastatin for System Suitability RS, dissolved first in Solution B, using 40% of the final volume, then diluted with Solution A to volume

Standard solution: 0.5 mg/mL of USP Fluvastatin Sodium RS, dissolved first in Solution B, using 40% of the final volume, then diluted with Solution A to volume

Sample solution: 0.5 mg/mL of Fluvastatin Sodium, dissolved first in Solution B, using 40% of the final volume, then diluted with Solution A to volume

3.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 305 nm

Column: 4.6-mm x 5-cm; 5-µm packing L1

Column temperature: 35°

Flow rate: 3 mL/min

Injection volume: 20 µL

[NOTE-Adjust the start time of the gradient step and the equilibration time for each instrument.]

3.3 System suitability

Samples: System suitability solution and Standard solution

[NOTE-The relative retention times for fluvastatin and fluvastatin anti-isomer are about 1.0 and 1.2, respectively.]

Suitability requirements

Resolution: NLT 1.6 between fluvastatin anti-isomer and fluvastatin, System suitability solution

Tailing factor: NMT 3.0 for the fluvastatin peak, System suitability solution

Relative standard deviation: NMT 0.73%, Standard solution

3.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of fluvastatin sodium (C₂₄H₂₅FNNaO₄) in the portion of Fluvastatin Sodium taken:

Result = (r_U/r_S) x (C_S/C_U) x 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

C_S = concentration of USP Fluvastatin Sodium RS in the Standard solution (mg/mL)

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

Acceptance criteria: 98.0%-102.0% on the anhydrous basis

4 IMPURITIES

ORGANIC IMPURITIES

[NOTE-Protect all solutions from light, and use amber autosampler vials and low-actinic glassware.]

Solution A, Solution B, Mobile phase, Standard solution, and Sample solution: Prepare as directed in the Assay.

System suitability solution A: Prepare as directed for the System suitability solution in the Assay.

System suitability solution B: 0.1 mg/mL of USP Fluvastatin Related Compound B RS in a mixture of methanol and acetonitrile (60:40).

Transfer about 0.5 mL of this solution to a 10-mL volumetric flask, and dilute with System suitability solution A to volume. [NOTE-System suitability solution B is stable for up to 6 months if stored in a refrigerator.]

Chromatographic system: Proceed as directed in the Assay, except for the Detector.

Detector

UV 365 nm: 3-Hydroxy-5-keto fluvastatin

UV 305 nm: For all other peaks

System suitability

Samples: Standard solution and System suitability solution B

Suitability requirements

Resolution: NLT 1.6 between fluvastatin anti-isomer and fluvastatin, System suitability solution B

Tailing factor: NMT 3.0 for the fluvastatin peak, System suitability solution B

Relative standard deviation: NMT 1.0% at 305 nm, Standard solution

Analysis

Samples: Standard solution and Sample solution

Record the chromatograms at 305 and 365 nm, identify the impurities listed in Table 2, and measure the peak responses. Calculate the percentage of each impurity, except for 3-hydroxy-5-keto fluvastatin, in the portion of Fluvastatin Sodium taken:

Result = (r_U/r_S) x (C_S/C_U) x (1/F) x 100

r_U = peak response at 305 nm of each impurity from the Sample solution

r_S = peak response at 305 nm of fluvastatin from the Standard solution

C_S = concentration of USP Fluvastatin Sodium RS in the Standard solution (mg/mL)

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

F = relative response factor (see Table 2)

Calculate the percentage of 3-hydroxy-5-keto fluvastatin in the portion of Fluvastatin Sodium taken:

Result = (r_U/r_S) x (C_S/C_U) x (1/F) x 100

r_U = peak response at 365 nm of 3-hydroxy-5-keto fluvastatin from the Sample solution

r_S = peak response at 365 nm of fluvastatin from the Standard solution

C_S = concentration of USP Fluvastatin Sodium RS in the Standard solution (mg/mL)

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

F = relative response factor (see Table 2)

Acceptance criteria: See Table 2.

Table 2

^a Sodium (3R,5S,E)-7-[1-ethyl-3-(4-fluorophenyl)-1H-indol-2-yl]-3,5-dihydroxyhept-6-enoate.

^b [R*R*-E]-(±)-7-[3-(4-Fluorophenyl)-1-(methylethyl)-1H-indol-2-yl]-3,5-dihydroxy-6-heptenoic acid monosodium salt; also known as Sodium (3RS,5RS,E)-7-(3-(4-fluorophenyl)-1-isopropyl-1H-indol-2-yl)-3,5-dihydroxyhept-6-enoate.

^c Sodium (E)-7-[3-(4-fluorophenyl)-1-isopropyl-1H-indol-2-yl]-3-hydroxy-5-oxohept-6-enoate.

^d At 365 nm.

^e Sodium (4E,6E)-7-[3-(4-fluorophenyl)-1-isopropyl-1H-indol-2-yl]-3-hydroxyhepta-4,6-dienoate.

^f 3-(4-Fluorophenyl)-1-isopropyl-1H-indole-2-carbaldehyde.

5 SPECIFIC TESTS

5.1 PH (791)

8.0-10.0, in a 10-mg/mL solution. Perform the test immediately after preparation.

5.2 WATER DETERMINATION (921), Method I

NMT 4.0%; if labeled as a hydrated form, NMT 12.0%. [NOTE-For this monograph, the term "hydrated form" refers to several known forms of fluvastatin sodium that are not stoichiometric hydrates.]

6 ADDITIONAL REQUIREMENTS

6.1 PACKAGING AND STORAGE

Preserve in tight, light-resistant containers, protected from moisture. Store at a temperature not exceeding 40°.

6.2 LABELING

Where it is a hydrated form, the label so indicates.

6.3 USP REFERENCE STANDARDS (11)

USP Fluvastatin Sodium RS

USP Fluvastatin Related Compound B RS

Fluvastatin t-butyl ester.

[R*,S*-E]-(±)-7-[3-(4-Fluorophenyl)-1-methylethyl-1H-indol-2-yl]-3,5-dihydroxy-6-heptenoic acid 1,1-dimethylethyl ester; also known as tert-Butyl (3RS,5SR,E)-7-[3-(4-fluorophenyl)-1-isopropyl-1H-indol-2-yl]-3,5-dihydroxyhept-6-enoate.

C₂₈H₃₄FNO₄ 467.58

USP Fluvastatin for System Suitability RS

Fluvastatin sodium, containing 1%-2% of the fluvastatin sodium anti-isomer.