Etoposide 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

Etoposide Capsules contain NLT 90.0% and NMT 110.0% of the labeled amount of etoposide (C₂₉H₃₂O₁₃).

[CAUTION-Etoposide is potentially cytotoxic. Great care should be taken to prevent inhaling particles of Etoposide and exposing the skin to it]

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (1927), Infrared Spectroscopy: 1978 (CN1-Mar-2020)

Sample: Transfer a suitable quantity of the contents of Capsules, equivalent to 100 mg of etoposide, to a separator containing 100 ml of water. Extract twice with 20-mL portions of chloroform, separate and combine the organic layers, dry over anhydrous sodium sulfate, and filter. Transfer the dried filtrate to a second separator, extract with 30 ml of water, and allow the layers to separate. Drain the chloroform layer through a bed of anhydrous sodium sulfate contained in a filter funnel into a round-bottom flask, and evaporate the chloroform at a temperature of 30±5° using a rotary evaporator. Dissolve the oily residue obtained in 5 mi, of water, shake gently, and allow to stand for 30 min. Filter, collecting the precipitate formed on a glass filter funnel, wash the precipitate with three 20-mL portions of water, and allow the precipitate to dry on the filter for about 90 min in a vacuum oven at 40°. Prepare a dispersion of the precipitate in potassium bromide at a ratio of 1 in 100

Acceptance criteria: Meet the requirements

B. 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

PROCEDURE

Buffer: 2.72 g/L of sodium acetate in water. Adjust with glacial acetic acid to a pH of 4.0.

Mobile phase: Acetonitrile and Buffer (26:74)

System suitability solution: 0.3 mg/mL of USP Etoposide Resolution Mixture RS in Mobile phase

Standard stock solution: 2.0 mg/mL of USP Etoposide RS in acetonitrile

Standard solution: 0.2 mg/ml of USP Etoposide RS in Mobile phase from the Standard stock solution

Sample stock solution: Transfer a sufficient number of Capsules, equivalent to 500 mg of etoposide, to a 500-ml volumetric flask, add about 400 ml, of Mobile phase, and stir using a magnetic bar for about 15 min, followed by sonication for about 1 h with occasional shaking. Cool, dilute with Mobile phase to volume, stir for an additional 5 min, and filter.

Sample solution: Equivalent to 0.2 mg/mL of Etoposide in Mobile phase from the Sample stock solution

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 3.9-mm × 30-cm; packing L11

Flow rate: 1 mL/min

Injection volume: 20 μL

Run time: NLT 1.5 times the retention time of etoposide

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 1.35 between the etoposide and a-etoposide peaks, System suitability solution

Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of etoposide (C₂₉H₃₂O₁₃) in the portion of Capsules taken:

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

r_U = peak response of etoposide from the Sample solution

r_S = peak response of etoposidefrom the Standard solution

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

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

Acceptance criteria: 90.0%-110.0%

4 PERFORMANCE TESTS

Medium: pH 45 acetate buffer, 900 ml

Apparatus 2: 50 rpm

Time: 30 min

Buffer: 2.72 g/l, of sodium acetate in water. Adjust with acetic acid to a pH of 4.0

Mobile phase: Acetonitrile and Buffer (26/74)

Standard solution: 55 µg/ml of USP Etccoside RS propand as follows. Transfer a quantity of LISE Blogoside RS to a suitable volumetric flask, and dissolve with sonication in methanol equivalent to 25% of the final volume. Dilute with Medium to volume.

Sample solution: Withraw a 10-ml, aliquot from the desolution vessel

Chromatographic system

(See Cheumatography (0211. System Sultanty)

Mode: LC

Detector: UV 240 nm

Column: 3.9-mm × 30-cm; packing L11

Flow rate: 2 mL/min

Injection volume 50

System suitability

Sample: Standard solution

Sultability requirements

Relative standard deviation: NMT 20%

Analysis

Samples: Standwe solution and Sample solubion

Calculate the percentage of the labeled amount of etoposide (C₂₉H₃₂O₁₃) dissolved.

Tolerance: NLT 80% (0) of the labeled amount of etoposide (C₂₉H₃₂O₁₃) is dissolved.

Uniformity of Dosage Units (905): Meet the requirements

5 IMPURITIES

Buffer: Prepare as directed in the Assay

Solution Ac Acetonitrile and Buffer (20:00)

Solution: Acetonstile and Buffer (60-40)

Mobile phase: See Table 1.

Standard stock solution: 20 mg/mL of USP Chongside RS in Diluent

System suitability stock solution: 0.1 mg/ml, of in-propylparaben in Diluent

System sultability solution: Transfer 5.0 mt of the System aultability stock solution and 5.0 mm of the Standard stock solution to a 50 en

volumetric flask, and dilute with Diluent to volume Transfer 5.0 ml of this solution to a 100-ml volumetric flack, and dilute with Diluent to volume

Standard solution: 10 pg/ml of JP Stonaside HS from the Standerd stock solution in piluwne

Sample solution: Nominally equivalent to 20 mg/mi. of stoposide in Diluent

Chromatographic system

(See Chromatoystem Suttate

Mode: LC

Detector: UV 254nm

Column: 3.9-mm × 15-cm; less than 5-μm packing L11

Flow rate: 1.5 mL/min

Injection volume: 25

Run time: NLT 40m

System sultability

Runtime is 15 min under isocratic conditi

Sample: System suitability solution

Suitability requirements

Resolution: NLT 1.1 between Propylparaben and etoposide

Analysis

Samples: Standard solution and Semple solution

Calculate the percentage of each impurity in the portion of Capsules taken:

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

r_U = peak response of each impurity from the Sample solution

r_S = peak response of etoposide from the Standard solution

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

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

Acceptance criteria: 500 Tab

Acceptance criteria: See Table 2.

6 ADDITIONAL REQUIREMENTS

PARADE AVE STORAGE: Preserve in tight containers in a cold place. Do not freeze.