Docetaxel 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

Docetaxel Injection is a sterile solution of Docetaxel. It contains NLT 90.0% and NMT 110.0% of the labeled amount of docetaxel (anhydrous) (C₄₃H₅₃NO₁₄). It contains Polysorbate 80 and/or other suitable solubilizing agents in the infusion vehicle. It may also contain dehydrated alcohol.

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: Water

Solution B: Acetonitrile

Mobile phase: See Table 1.

Table 1

Diluent: Acetonitrile, glacial acetic acid, and water (100:0.1:100)

System suitability solution: 1 mg/mL of USP Docetaxel Identification RS in Diluent

Standard solution: 0.2 mg/mL of USP Docetaxel RS. Transfer USP Docetaxel RS into a suitable volumetric flask, and dissolve in alcohol equivalent to 5% of the final volume. Dilute with Diluent to volume.

Sample solution (for Injection labeled as one-vial formulation): Dilute a portion of the Injection with Diluent to obtain a solution containing 0.2 mg/mL of docetaxel (anhydrous).

Sample solution (for Injection labeled as two-vial formulation): Transfer the content of the vial containing the Injection concentrate to a suitable volumetric flask. Dissolve in an amount of alcohol equivalent to 5% of the final volume, and dilute with Diluent to volume to obtain a solution having a concentration of 0.2 mg/mL of docetaxel (anhydrous).

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 232 nm. For Identification B, use a diode array detector.

Column: 4.6-mm × 15-cm; 3.5-μm packing L1

Temperatures

Refrigerated autosampler: 10°

Column: 45°

Flow rate: 1.2 mL/min

Injection volume: 20 μL

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 3.5 between 2-debenzoxyl 2-pentenoyl docetaxel and docetaxel, System suitability solution

Relative standard deviation: NMT 1.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of docetaxel (C₄₃H₅₃NO₁₄) in the portion of Injection taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U= peak area from the Sample solution

r_S= peak area from the Standard solution

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

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

Acceptance criteria: 90.0%–110.0%

4 IMPURITIES

Organic Impurities

Mobile phase, Diluent, System suitability solution, Standard solution, Sample solution, and Chromatographic system: Proceed as directed in the Assay.

Sensitivity solution: 0.2 μg/mL of USP Docetaxel RS in Diluent from the Standard solution

System suitability

Samples: System suitability solution, Standard solution, and Sensitivity solution

Suitability requirements

Resolution: NLT 3.5 between 2-debenzoxyl 2-pentenoyl docetaxel and docetaxel, System suitability solution

Relative standard deviation: NMT 1.0%, Standard solution

Signal-to-noise ratio: NLT 10 for the docetaxel peak, Sensitivity solution

Analysis

Sample: Sample solution

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

Result = (r_U/r_T) × (1/F) × 100

r_U= peak area of each individual impurity from the Sample solution

r_T= sum of all of the peak areas from the Sample solution

F = relative response factor for each individual impurity (see Table 2)

Acceptance criteria: See Table 2. Disregard any impurity peak less than 0.1% and any peak with a relative retention time less than 0.2 or greater than 1.3.

Table 2

^a (2aR,4S,4aS,6R,9S,11S,12S,12aR,12bS)-1,2a,3,4,4a,6,9,10,11,12,12a,12b-Dodecahydro-4,6,9,11,12,12b-hexahydroxy-4a,8,13,13-tetramethyl-7,11-methano-5H-cyclodeca[3,4]benz[1,2-b]oxet-5-one 12b-acetate,12-benzoate.

^b (2aR,4S,4aS,6R,9S,11S,12S,12aR,12bS)-1,2a,3,4,4a,6,9,10,11,12,12a,12b-Dodecahydro-4,6,9,11,12,12b-hexahydroxy-4a,8,13,13-tetramethyl-7,11-methano-5H-cyclodeca[3,4]benz[1,2-b]oxet-5-one 12b-acetate,12-[(E)-2-methylbut-2-enoate], 9-ester with (2R,3S)-N-tert-butoxycarbonyl-3-phenylisoserine. The alternative chemical name is 5β,20-Epoxy-1,7β,10β-trihydroxy-9-oxotax-11-ene-2α,4,13α-triyl 4-acetate 13-[(2R,3S)-3-[[(1,1-dimethylethoxy)carbonyl]amino]-2-hydroxy-3-phenylpropanoate] 2-[(2E)-2-methylbut-2-enoate]. It is a process impurity and is listed in Table 2 for identification only. It is controlled in the drug substance. It is not reported for the drug product and should not be included in the total impurities.

^c (1S,2S,3R,9S,E)-3-[(S,E)-2-Acetoxy-1-hydroxy-5-oxopent-3-en-2-yl]-1,5,9-trihydroxy-4,8,11,11-tetramethyl-6-oxobicyclo[5.3.1]undeca-4,7-dien-2-yl benzoate, 9-ester with (2R,3S)-N-tert-butoxycarbonyl-3-phenylisoserine.

^d (2aR,4S,4aS,9S,11S,12S,12aR,12bS)-1,2a,3,4,4a,6,9,10,11,12,12a,12b-Dodecahydro-4, 9,11,12,12b-pentahydroxy-4a,8,13,13-tetramethyl-7,11-methano-5H-cyclodeca[3,4]benz[1,2-b]oxet-5,6-dione 12b-acetate, 12-benzoate, 9-ester with (2R,3S)-N-tert-butoxycarbonyl-3-phenylisoserine. The alternative chemical name is 5β,20-Epoxy-1,7β-dihydroxy-9,10-dioxotax-11-ene-2α,4,13α-triyl 4-acetate 2-benzoate 13-[(2R,3S)-3-[[(1,1-dimethylethoxy)carbonyl]amino]-2-hydroxy-3-phenylpropanoate].

^e (2aR,4R,4aS,6R,9S,11S,12S,12aR,12bS)-1,2a,3,4,4a,6,9,10,11,12,12a,12b-Dodecahydro-4,6,9,11,12,12b-hexahydroxy-4a,8,13,13-tetramethyl-7,11-methano-5H-cyclodeca[3,4]benz[1,2-b]oxet-5-one 12b-acetate,12-benzoate, 9-ester with (2R,3S)-N-tert-butoxycarbonyl-3-phenylisoserine. The alternative chemical name is 5β,20-Epoxy-1,7α,10β-trihydroxy-9-oxotax-11-ene-2α,4,13α-triyl 4-acetate 2-benzoate 13-[(2R,3S)-3-[[(1,1-dimethylethoxy)carbonyl]amino]-2-hydroxy-3-phenylpropanoate].

^f (2aR,4R,4aS,9S,11S,12S,12aR,12bS)-1,2a,3,4,4a,6,9,10,11,12,12a,12b-Dodecahydro-4, 9,11,12,12b-pentahydroxy-4a,8,13,13-tetramethyl-7,11-methano-5H-cyclodeca[3,4]benz[1,2-b]oxet-5,6-dione 12b-acetate, 12-benzoate, 9-ester with (2R,3S)-N-tert-butoxycarbonyl-3-phenylisoserine. The alternative chemical name is 5β,20-Epoxy-1,7α-dihydroxy-9,10-dioxotax-11-ene-2α,4,13α-triyl 4-acetate 2-benzoate 13-[(2R,3S)-3-[[(1,1-dimethylethoxy)carbonyl]amino]-2-hydroxy-3-phenylpropanoate].

5 SPECIFIC TESTS

Bacterial Endotoxins Test 〈85〉: It contains NMT 1.94 USP Endotoxin Units/mg of docetaxel (anhydrous).

Sterility Tests 〈71〉, Test for Sterility of the Product to Be Examined, Membrane Filtration: Meets the requirements

Particulate Matter in Injections 〈788〉: Meets the requirements for small-volume injections

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

6 ADDITIONAL REQUIREMENTS

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

Labeling: Label it to indicate whether it is a one-vial formulation or two-vial formulation (Injection concentrate and diluent), and also label it to indicate that it is to be diluted with a suitable parenteral vehicle before intravenous infusion.

USP Reference Standards 〈11〉

USP Docetaxel RS

USP Docetaxel Identification RS

[Note—USP Docetaxel Identification RS contains docetaxel and small amounts of 2-debenzoxyl 2-pentenoyl docetaxel, 6-oxodocetaxel, 4-epidocetaxel, and 4-epi-6-oxodocetaxel.]