Paclitaxel 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

Paclitaxel Injection is a sterile, stabilized solution of Paclitaxel, suitable for dilution for intravenous administration. It contains NLT 90.0% and NMT 110.0% of the labeled amount of paclitaxel (C₄₇H₅₁NO₁₄).

2 IDENTIFICATION

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A. 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-May-2021)

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

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Procedure

Diluent: To a volumetric flask, add 50% of the flask volume of methanol and then add 0.02% of the flask volume of acetic acid, glacial. Dilute with methanol to volume.

Mobile phase: Acetonitrile and water (45:55)

Standard solution: 0.6 mg/mL of USP Paclitaxel RS in Diluent

Sample solution: Nominally 0.6 mg/mL of paclitaxel from Injection in Diluent

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 227 nm. For Identification A, use a diode array detector in the range of 200–400 nm. (USP 1-May-2021)

Column: 4.0-mm × 25-cm; 5-μm packing L43

Flow rate: 1.5 mL/min

Injection volume: 10 μL

System suitability

Sample: Standard solution

Suitability requirements

Retention time: 6.0–10.0 min

Relative standard deviation: NMT 1.5%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of paclitaxel (C₄₇H₅₁NO₁₄) in the portion of Injection taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of paclitaxel from the Sample solution

r_S = peak response of paclitaxel from the Standard solution

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

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

Acceptance criteria: 90.0%–110.0%

4 IMPURITIES

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Organic Impurities

Solution A: Acetonitrile and water (40:60)

Solution B: Acetonitrile

Mobile phase: See Table 1.

Table 1

Standard solution: 1.2 mg/mL of USP Paclitaxel RS and 0.006 mg/mL of USP Paclitaxel Related Compound B RS in acetonitrile

Sample solution: Nominally 1.2 mg/mL of paclitaxel from Injection in acetonitrile

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 227 nm

Column: 4.6-mm × 15-cm; 3-μm packing L1

Column temperature: 35°

Flow rate: 1.2 mL/min

Injection volume: 10 μL

System suitability

Sample: Standard solution

[Note - See Table 2 for the relative retention times.]

Suitability requirements

Resolution: NLT 1.2 between the paclitaxel related compound B and paclitaxel peaks

Relative standard deviation: NMT 2.0% for paclitaxel (USP 1-May-2021)

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each degradation product in the portion of Injection taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of each degradation product from the Sample solution

r_S = peak response of paclitaxel related compound B from the Standard solution

C_S = concentration of USP Paclitaxel Related Compound B RS in the Standard solution (mg/mL)

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

Acceptance criteria: See Table 2.

Table 2

^a(2aR,4S,4aS,6R,9S,11S,12S,12aR,12bS)-12-(Benzoyloxy)-4,9,11-trihydroxy-4a,8,13,13-tetramethyl-5-oxo-3,4,4a,5,6,9,10,11,12,12a- decahydro-1H-7,11-methanocyclodeca[3,4]benzo[1,2-b]oxete-6,12b(2aH)-diyl diacetate.

^b Ethyl (2R,3S)-3-benzamido-2-hydroxy-3-phenylpropanoate.

^c(2aR,4S,4aS,6R,9S,11S,12S,12bS)-12b-Acetoxy-9-(((2R,3S)-3-benzamido-2-hydroxy-3-phenylpropanoyl)oxy)-4,6,11-trihydroxy-4a,8,13,13-tetramethyl-5-oxo-2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-1H-7,11-methanocyclodeca[3,4]benzo[1,2-b]oxet-12-yl benzoate.

^d(2aR,4R,4aS,6R,9S,11S,12S,12bS)-9-(((2R,3S)-3-Benzamido-2-hydroxy-3-phenylpropanoyl)oxy)-12-(benzoyloxy)-4,11-dihydroxy-4a,8,13,13-tetramethyl-5-oxo-3,4,4a,5,6,9,10,11,12,12a-decahydro-1H-7,11-methanocyclodeca[3,4]benzo[1,2-b]oxete-6,12b(2aH)-diyl diacetate.

5 SPECIFIC TESTS

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Bacterial Endotoxins Test 〈85〉: Meets the requirements (USP 1-May-2021)

pH 〈791〉

Sample: 1 in 10

Acceptance criteria: 3.0–7.0

Other Requirements: It meets the requirements in Injections and Implanted Drug Products 〈1〉.

6 ADDITIONAL REQUIREMENTS

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Packaging and Storage: Preserve in single-dose or multiple-dose containers, preferably of Type I glass, at controlled room temperature.

Protect from light. (USP 1-May-2021)

Labeling: Label it to indicate that it is to be diluted with a suitable parenteral vehicle before intravenous infusion.

Change to read:

USP Reference Standards 〈11〉

USP Paclitaxel RS

USP Paclitaxel Related Compound B RS

10-Deacetyl-7-epipaclitaxel.

C₄₅H₄₉O₁₃N 811.87