Fluvastatin Capsules

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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1 DEFINITION

Fluvastatin Capsules contain fluvastatin sodium (C₂₄H₂₅FNNaO₄) equivalent to NLT 90.0% and NMT 110.0% of the labeled amount of fluvastatin (C₂₄H₂₆FNO₄).

2 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.

Add the following:

B. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay. (USP 1-Aug-2019)

3 ASSAY

Change to read:

3.1 PROCEDURE

[NOTE-Protect all solutions from light.] (USP 1-AUG-2019)

Buffer: Prepare a solution containing 40 mL of 25% aqueous tetramethylammonium hydroxide in 1 L of water. Adjust with approximately 4.5 mL of phosphoric acid to a pH of 7.2.

Solvent mixture: Methanol and acetonitrile (60:40)

Solution A: Solvent mixture and Buffer (12.5:87.5)

Solution B: Solvent mixture and Buffer (87.5:12.5)

Mobile phase: See Table 1. (USP 1-Aug-2019)

Table 1

Diluent: Solvent mixture and Buffer (46:54)

System suitability solution: 0.42 mg/mL of fluvastatin sodium from USP Fluvastatin for System Suitability RS in Diluent

Standard solution: 0.42 mg/mL of USP Fluvastatin Sodium RS, equivalent to 0.4 mg/mL of fluvastatin, in Diluent

Sample stock solution: Nominally 1.0 mg/mL of fluvastatin from Capsules prepared as follows. Transfer the contents and the empty shells of a suitable number of (USP 1-Aug-2019) Capsules, equivalent to 200 mg of fluvastatin, to a 200-mL volumetric flask. Add 100 mL of methanol, and stir with a magnetic or mechanical stirrer for 45 min. Centrifuge a portion of this solution at 4000 rpm for 20 min.

Sample solution: Nominally 0.4 mg/mL of fluvastatin from Sample stock solution in Diluent

3.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 305 nm. For Identification B, use a diode array detector in the range of 200-400 nm. (USP 1-Aug-2019)

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

Flow rate: 2.0 mL/min

Injection volume: 25 µL (USP 1-Aug-2019)

3.3 System suitability

Samples: System suitability solution and Standard solution (USP 1-Aug-2019) [NOTE-The relative retention times for fluvastatin and fluvastatin anti-isomer are 1.0 and 1.2, respectively.]

Suitability requirements

Resolution: NLT 1.4 between fluvastatin anti-isomer and fluvastatin, System suitability solution (USP 1-Aug-2019)

Relative standard deviation: NMT 1.5%, Standard solution (USP 1-Aug-2019)

3.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of fluvastatin (C₂₄H₂₆FNO₄) in the portion of Capsules taken:

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

r_U = peak response of fluvastatin from the Sample solution

r_S = peak response of fluvastatin from the Standard solution

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

C_U = nominal concentration of fluvastatin in the Sample solution (mg/mL)

M_r1 = molecular weight of fluvastatin, 411.47 (USP 1-Aug-2019)

M_r2 = molecular weight of fluvastatin sodium, 433.45

Acceptance criteria: 90.0%-110.0%

4 PERFORMANCE TESTS

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4.1 DISSOLUTION (711)

Medium: Water: 500 mL

Apparatus 2: 50 rpm, sinkers not used

Time: 30 min

(USP 1-Aug-2019)

Buffer: 1.534 g of monobasic ammonium phosphate in 800 mL of water. Adjust with phosphoric acid or ammonium hydroxide to a pH of 3.5.

Mobile phase: Methanol and Buffer (7:3)

Standard solution: (0.002 x L) mg/mL of USP Fluvastatin Sodium RS in Medium, where L is the label claim in mg/Capsule (USP 1-Aug-2019) [NOTE-A volume of methanol, not exceeding 2% of the final volume of solution, may be used to aid in dissolving USP Fluvastatin Sodium RS.]

Sample solution: Pass a portion of the solution under test through a suitable filter, discarding the first 2 mL of the filtrate.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 235 nm

Columns

Guard: 3.2-mm x 1.5-cm; (USP 1-Aug-2019) 7-µm packing L1

Analytical: 4.6-mm x 10-cm; 5-um packing L1

Flow rate: 2.0 mL/min

Injection volume: 50 µL

System suitability

Sample: Standard solution

Suitability requirements

Relative standard deviation: NMT 1.5%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of fluvastatin (C₂₄H₂₆FNO₄) dissolved:

Result = (r_U/r_S) x C_S x V x (M_r1/M_r2) x 100

r_U = peak response of fluvastatin from the Sample solution

r_S = peak response of fluvastatin from the Standard solution

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

V = volume of Medium, 500 mL

L = label claim (mg/Capsule)

M_r1 = molecular weight of fluvastatin, 411.47

M_r2 = molecular weight of fluvastatin sodium, 433.45

(USP 1-Aug-2019)

Tolerances: NLT 80% (Q) of the labeled amount of fluvastatin (C₂₄H₂₆FNO₄) is dissolved.

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4.2 UNIFORMITY OF DOSAGE UNITS (905)

Meet the requirements (USP 1-Aug-2019)

5 IMPURITIES

Change to read:

ORGANIC IMPURITIES

(USP 1-Aug-2019)

Buffer, Solvent mixture, Solution A, Solution B, Mobile phase, Diluent, System suitability solution, Standard solution, and Sample solution: Prepare as directed in the Assay.

Sensitivity solution: 0.21 µg/mL of USP Fluvastatin Sodium RS in Diluent, from Standard solution (USP 1-Aug-2019)

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

Detector

UV 365 nm: For 3-hydroxy-5-keto fluvastatin

UV 305 nm: For all the other impurities

System suitability

Samples: System suitability solution, Standard solution, and Sensitivity solution (USP 1-Aug-2019)

Suitability requirements

Resolution: NLT 1.4 between fluvastatin anti-isomer and fluvastatin, System suitability solution

Relative standard deviation: NMT 1.5%, Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution (USP 1-Aug-2019)

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each degradation product (USP 1-Aug-2019) in the portion of Capsules taken:

Result = (r_U/r_S) x (C_S/C_U) x (M_r1/M_r2) x (1/F) x 100

r_U = peak response of each degradation product (USP 1-Aug-2019) from the Sample solution

r_S = peak response of fluvastatin from the Standard solution

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

C_U = nominal concentration of fluvastatin in the Sample solution (mg/mL)

M_r1 = molecular weight of fluvastatin, 411.47 (USP 1-Aug-2019)

M_r2 = molecular weight of fluvastatin sodium, 433.45

F = relative response factor (see Table 2)

(USP 1-Aug-2019)

Acceptance criteria: See Table 2. The reporting threshold is 0.05%. (USP 1-Aug-2019)

Table 2

^a Sodium (3RS, 5RS,E)-7-(3-(4-fluorophenyl)-1-isopropyl-1H-indol-2-yl)-3,5-dihydroxyhept-6-enoate.

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

^c At 365 nm.

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

^e 3-(4-Fluorophenyl)-1-(methylethyl)-1H-indole-2-carboxaldehyde.

6 ADDITIONAL REQUIREMENTS

6.1 PACKAGING AND STORAGE

Preserve in tight, light-resistant containers, protected from moisture and from light. Store in a cool place or at controlled room temperature.

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6.2 USP REFERENCE STANDARDS (11).

USP Fluvastatin Sodium RS

USP Fluvastatin for System Suitability RS

Fluvastatin sodium, containing 1%-2% of the fluvastatin sodium anti-isomer. (USP 1-Aug-2019)