Etoposide Phosphate for Injection

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 Phosphate for Injection is sterile, lyophilized powder of Etoposide Phosphate and suitable added substances. It contains NLT 90% and NMT 105% of the labeled amount of etoposide phosphate (C₂₉H₃₃O₁₆P).

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

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

B. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

PROCEDURE

Solution A: 2.3 g/L of ammonium phosphate, monobasic in water

Mobile phase: Acetonitrile and Solution A (15:85). Adjust with phosphoric acid to a pH of 2.5.

Standard solution: 0.24 mg/mL of USP Etoposide Phosphate RS in Mobile phase. Sonicate to assist with dissolution.

Sample solution: Nominally equivalent to 0.24 mg/ml of etoposide phosphate in Mobile phase from Etoposide Phosphate for Injection.

Sonicate to assist with dissolution.

Chromatographic system

(See Chromatography (621) System Suitability)

Mode: LC

Detector: UV 230 nm. For Identification B, use a diode array detector in the range of 190-400 nm.

Column: 4.6-mm × 15-cm; 5-μm packing L11

Flow rate: 1.5 mL/min

Injection volume: 25 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 1.5

Relative standard deviation: NMT 1.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of etoposide phosphate (C₂₉H₃₃O₁₆P) in the portion of Etoposide Phosphate for Injection taken:

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

r_U = peak response of etoposide phosphate from the Sample solution

r_S = peak response of etoposide phosphate from the Standard solution

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

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

Acceptance criteria: 90%-105%

4 PERFORMANCE TESTS

Uniformity of Dosage Units (905): Meets the requirements.

IMPURITIES

Mobile phase, Sample solution, and Chromatographic system: Proceed as directed in the Assay

Standard stock solution A: Use the Standard solution in the Assay

Standard solution A: 2.4 µg/ml of USP Etoposide Phoachate BS in Mobile phase, from Standard stock solution A

Standard stock solution B: 0.024 mg/ml of US Conomide RSS accionitnit

Standard solution B: 48 µg/ml, of USP Etupusite RS in Mobile phane

Sensitivity selution: 0.24 pg/ml. of LSP Etoposide Phosphate 35 in Mobile phase, from Standard solution

System suitability

Samples: Standard solution A Standard solution at and Sensitivity solution

Suitability requirements

Relative standard deviation: NMT 10% for etoposide phciphate and empie Standard solution A and Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution

Analysis

Samples: Sample sottot, Standard solution A, and Standard solution

Calculate the percentage of etoposide in the portion of Etoposide Phosphate for Injection taken:

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

r_U = peak area of etoposide from the Sample solution

r_S = peak area of etoposide from the Standard solution

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

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

Calculate the percentage of lignan Pphosphate and each individual unspecified impurity in the portion of Etoposide Phosphate for Injection taken:

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

r_U = peak area of lignan P phosphate and each individual unspecified impurity from the Sample solution

r_S = ppeak area of etoposide phosphate from Standard solution A

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

C_U = ominal concentration of etoposide phosphate in the Sample solution (mg/mL)

F = relative response factor (see Table 1) 

Acceptance criteria: Sec Table 1

^a (5R,5aR,8aR,9S)-9-[β-d-Glucopyranosyloxy]-5,8,8a,9-tetrahydro-5-[3,5-dimethoxy-4-(phosphonooxy)phenyl]furo[3’,4’:6,7]naphtho[2,3-d]-1,3-dioxol-6(5aH)-one.

5 SPECIFIC TESTS

Bacterial Endotoxins Test (85): Meets the requirements

• Sterility Tests (71): Meets the requirements

• Particulate Matter in Injections (788): Meets the requirements for small-volume injections

• pH (791)

Sample solution: A constituted solution prepared as directed in the labeling

Acceptance criteria: 4.0–5.0

• Other Requirements: Meets the requirements in Injections and Implanted Drug Products 〈1〉

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve as directed in Packaging and Storage Requirements 〈659〉, Injection Packaging, Packaging for Constitution.

Store at 2°–8° and protect from light.