Cyclophosphamide Tablets

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

Cyclophosphamide Tablets contain Cyclophosphamide equivalent to NLT 90.0% and NMT 110.0% of the labeled amount of anhydrous cyclophosphamide (C₇H₁₅CI₂N₂O₂P).

2 IDENTIFICATION

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A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K _{▲(CN 1-MAY-2020)}

Sample: Extract a portion of finely powdered Tablets, equivalent to 50 mg of cyclophosphamide, with 25 mL of chloroform. Filter about 2 mL of the chloroform solution, mix the filtrate with 500 mg of potassium bromide, evaporate the chloroform, carefully removing the last trace of solvent in a small vacuum flask, and use the residue to prepare a potassium bromide dispersion.

Acceptance criteria: The IR absorption spectrum of the Sample exhibits maxima, between 6.5 and 14 µm, only at the same wavelengths as those of a similar preparation of USP Cyclophosphamide RS.

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

3.1 PROCEDURE

Mobile phase: Acetonitrile and water (30:70)

Ethylparaben solution: Dissolve 185 mg of ethylparaben in 250 ml of alcohol in a 1000-ml volumetric flask, and dilute with water to volume.

System suitability solution: 0.5 mg/mL of USP Cyclophosphamide RS and 0.0185 mg/mL of ethylparaben in water prepared as follows.

Transfer a quantity of USP Cyclophosphamide RS to a suitable volumetric flask, add water equivalent to 50% of the final volume, and shake to dissolve. Add Ethylparaben solution equivalent to 10% of the final volume, and dilute with water to volume.

Standard solution: 0.5 mg/mL of USP Cyclophosphamide RS in water

Sample solution: Nominally equivalent to 0.5 mg/mL of anhydrous cyclophosphamide prepared as follows. Transfer NLT 10 Tablets to a suitable volumetric flask. Fill about half full with water shake for 30 min, and dilute with water to volume. Pass through fast, fluted filter paper, and discard the first 40-50 mL of the filtrate.

3.1.1 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 195 nm

Column: 3.9-mm x 30-cm; packing 11

Flow rate: 1.5 mL/min

Injection volume: 25 µL

3.1.2 System suitability

Samples: System suitability solution and Standard solution

[NOTE-The relative retention times for cyclophosphamide and ethylparaben are 0.7 and 1.0, respectively.]

3.1.3 Suitability requirements

Resolution: NLT 2 between cyclophosphamide and ethylparaben, System suitability solution

Relative standard deviation: NMT 2% from six replicate injections, Standard solution

3.1.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of anhydrous cyclophosphamide (C₇H₁₅CI₂N₂O₂P) in the portion of Tablets taken:

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

r_U = peak response of cyclophosphamide from the Sample solution

r_S = peak response of cyclophosphamide from the Standard solution r_{s} = 1

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

C_U = nominal concentration of anhydrous cyclophosphamide in the Sample solution (mg/mL) Cu

Acceptance criteria: 90.0%-110.0%

4 PERFORMANCE TESTS

4.1 DISSOLUTION (71.1).

Medium: Water: 900 mL, deaerated

Apparatus 1: 100 rpm

Time: 45 min

Mobile phase: Acetonitrile and water (30:70)

Standard solution: USP Cyclophosphamide RS in water at a concentration similar to that of the Sample solution

Sample solution: Pass a portion of solution under test through a suitable filter of 0.8-µm pore size.

4.1.1 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 195 nm

Column: 3.9-mm x 30-cm; packing 11

Flow rate: 1.5 mL/min

Injection volume: 50 µL

4.1.2 System suitability

Sample: Standard solution

4.1.3 Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

4.1.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of anhydrous cyclophosphamide (C₇H₁₅CI₂N₂O₂P) dissolved:

                 Result = (r_U/r_S) x C_S x V x (1/L) x 100

r_U = peak response of cyclophosphamide from the Sample solution

r_S = peak response of cyclophosphamide from the Standard solution

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

V = volume of Medium, 900 mL

L = label claim (mg/Tablet)

Tolerances: NLT 75% (Q) of the labeled amount of anhydrous cyclophosphamide (C₇H₁₅CI₂N₂O₂P) is dissolved.

4.2 UNIFORMITY OF DOSAGE UNITS (905):

Meet the requirements

5 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers. Storage at a temperature not exceeding 25° is recommended. Tablets will withstand brief exposure to temperatures up to 30° but are to be protected from temperatures above 30".

USP REFERENCE STANDARDS (11)

USP. Cvelenhosphamide RS