Etoposide

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

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

DOWNLOAD PDF HERE

Furo[3′,4′:6,7]naphtho[2,3-d]-1,3-dioxol-6(5aH)-one-, 9-[(4,6-O-ethylidene-β-d-glucopyranosyl)oxy]5,8,8a,9-tetrahydro-5-(4-hydroxy-3,5-

dimethoxyphenyl), [5R-[5α,5aβ,8aα,9β(R*)]]-;

4′-Demethylepipodophyllotoxin 9-[4,6-O-(R)-ethylidene-β-d-glucopyranoside] CAS RN^®: 33419-42-0; UNII: 6PLQ3CP4P3.

1 DEFINITION

Etoposide contains NLT 95.0% and NMT 105.0% of etoposide (C₂₉H₃₂O₁₃), calculated on the anhydrous basis.

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

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopic 197K 

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: 2.0 mg/mL of Etoposide in acetonitrile

Sample solution: 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: Stanciard solution and Sample solution

Calculate the percentage of etoposide (C₂₉H₃₂O₁₃) in the portion of Etoposide 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 etoposide from 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: 95.0-100.0% on the anhydrous basis

4 IMPURITIES

Residue on Ignition (281): NMT-0.1%

Buffer: Prepare as directed in the Assay

Solution Ac Acetonitrile and Buffer (2080)

Solution B: Acetonitrile and Buffer (00:40)

Mobile phase: See Table 1.

Diluent: Acetonitle and 0:02 M sodium acetate previously adjusted with acetic acid to a pH of 4.0 (30:70)

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

System suitability stock solution: 0.2 mg/ml of in Propylparaben in Diluent

System suitability solution: Transfer 1.0 ml. of the System suitability stook sution and 50 mL of the Standard stuck sulution to a 30 volumetric flask, and dilute with Diluent to volume. Transfer 3.0 ml, of this solution to a 100-ml volumetric flask, and dilute with plent to volume

Standard solution: 10 µg/mt. of USP Paaside RS from the Standard stock solution in Ent

Sample solution: 20 mg/ml of Etoposiden Dint

Chromatographic system

(See Chromatogrant/211 Stem Sudabit)

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 μL

Run time: NLT 40 min

System suitability

Nor-Run time is 15 min in isocratic conditions

Sample: System surtatility aution

Sultability requirements

Resolution: NLT 1.1 between propylparaben and etoposide

Analysis

Samples: Stand solution and lample solution

Cafoulate the percentage of each impurity in the portion of Etoposide 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 = concentration of Etoposide in the Sample solution (mg/mL)

Acceptance criterlac See Table 2

5 SPECIFIC TESTS

Optical Rotation, Specific Rotation (781S)

Sample solution: 5 mg/mL in chloroform and methanol (9:1)

Acceptance criteria: −110° to −118° (t = 20°)

• Water Determination, Method I〈921〉: NMT 6.0%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight, light-resistant containers.