Docetaxel

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 contains NLT 97.5% and NMT 102.0% of docetaxel (C₄₃H₅₃NO₁₄), calculated on the anhydrous and solvent-free basis. [Caution—Docetaxel is cytotoxic. Great care should be taken to prevent inhaling particles of Docetaxel and exposing the skin to it.]

2 IDENTIFICATION

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197A, 197K, 197M, or 197S

[Note—Use a solution containing 60 mg/mL of Docetaxel in methylene chloride for 〈197S〉.]

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

Solution A: Water

Solution B: Acetonitrile

Mobile phase: See Table 1.

Table 1

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

System suitability solution: 1 mg/mL of USP Docetaxel Identification RS in Diluent. [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. See Table 2.]

Standard solution: 1.0 mg/mL of USP Docetaxel RS prepared as follows. Transfer a quantity of USP Docetaxel RS to a suitable volumetric flask, dissolve in alcohol equivalent to about 5% of the final volume, and dilute with Diluent to volume.

Sample solution: 1.0 mg/mL of Docetaxel prepared as follows. Transfer a quantity of Docetaxel to a suitable volumetric flask, dissolve in alcohol equivalent to about 5% of the final volume, and dilute with Diluent to volume.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 232 nm

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

Temperatures

Autosampler: 10°

Column: 45°

Flow rate: 1.2 mL/min

Injection volume: 10 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 docetaxel (C₄₃H₅₃NO₁₄) in the portion of Docetaxel taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U= peak response from the Sample solution

r_S= peak response from the Standard solution

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

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

Acceptance criteria: 97.5%–102.0% on the anhydrous and solvent-free basis

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.1%

Change to read:

Organic Impurities, Procedure 1

[Note—On the basis of the synthetic route, perform either Procedure 1 or Procedure 2. Procedure 1 is recommended if 10-deacetyl baccatin and 2-debenzoxyl 2-pentenoyl docetaxel are specified impurities. Procedure 2 is recommended if O-BOC N-pyruvyl docetaxel is a specified impurity.]

Mobile phase, Diluent,(ERR 1-Jun-2024) System suitability solution, Standard solution, Sample solution, and Chromatographic system: Proceed as directed in the Assay.

Sensitivity solution: 0.5 μg/mL of USP Docetaxel RS in Diluent from the Standard solution

System suitability

Samples: System suitability solution and Sensitivity solution

Suitability requirements

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

Result = (r_U/r_T) × (1/F) × 100

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

r_T= sum of all peak responses from the Sample solution

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

Acceptance criteria: See Table 2. Disregard any peaks less than 0.05%.

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 If possible from the manufacturing process.

^c (2aR,4S,4aS,6R,9S,11S,12S,12aR,12bS)-12b-Acetoxy-9-(((2R,3S)-3-formamido-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,4S,4aS,6R,9S,11S,12S,12aR,12bS)-6-{[(2,2-Dichloroethoxy)carbonyl]oxy}-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-one 12b-acetate, 12-benzoate, 9-ester with (2R,3S)-N-tert-butoxycarbonyl-3-phenylisoserine.

Organic Impurities, Procedure 2

Solution A: Water

Solution B: Acetonitrile

Mobile phase: See Table 3.

Table 3

System suitability solution: 1 mg/mL of USP Docetaxel System Suitability Mixture RS in acetonitrile. [Note—USP Docetaxel System Suitability

Mixture RS contains docetaxel and a small amount of 6-oxodocetaxel, O-BOC N-pyruvyl docetaxel, 4-epidocetaxel, and 4-epi-6-oxodocetaxel. See Table 4.]

Standard solution: 5.0 μg/mL of USP Docetaxel RS in acetonitrile

Sample solution: 1.0 mg/mL of Docetaxel in acetonitrile

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 230 nm

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

Temperatures

Column: 40°

Sample: 4°

Flow rate: 1.2 mL/min

Injection volume: 10 μL

System suitability

Sample: System suitability solution

Suitability requirements

Resolution: NLT 2.0 between O-BOC N-pyruvyl docetaxel and 4-epidocetaxel

Tailing factor: 0.8–1.5 for the docetaxel peak

Analysis

Samples: Standard solution and Sample solution

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

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

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

r_S= peak area of docetaxel from the Standard solution

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

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

F = relative response factor for each individual impurity (see Table 4)

Acceptance criteria: See Table 4. Disregard any peaks less than 0.05%.

Table 4

^a (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)-2-(tert-butoxycarbonyloxy)-3-(2-oxopropanamido)-3-phenylpropanoic acid.

5 SPECIFIC TESTS

Microbial Enumeration Tests 〈61〉andTests for Specified Microorganisms 〈62〉: The total aerobic microbial limit does not exceed 102cfu/g. The total molds and yeasts count does not exceed 10 cfu/g.

Bacterial Endotoxins Test 〈85〉: It contains NMT 0.4 USP Endotoxin Units/mg.

Water Determination 〈921〉, Method I, Method Ic: 5.0%–7.0%. If labeled as an anhydrous form: NMT 1.5%.

Optical Rotation 〈781S〉, Procedures, Specific Rotation

Sample solution: 10 mg/mL in methanol

Acceptance criteria: −39° to −41° (t = 20°), calculated on the anhydrous and solvent-free basis. If labeled as an anhydrous form: −35° to −45° (t = 20°), calculated on the as-is basis.

6 ADDITIONAL REQUIREMENTS

Labeling: Where it is an anhydrous form, the label so indicates. If a test for Organic Impurities other than Procedure 1 is used, the labeling states the test with which the article complies.

Packaging and Storage: Preserve in well-closed, light-resistant containers, and store at room temperature or between 2° and 8°.

USP Reference Standards 〈11〉

USP Docetaxel RS

USP Docetaxel Identification RS

It contains docetaxel and small amounts of the following:

2-Debenzoxyl 2-pentenoyl docetaxel: (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.

C₄₁H₅₅NO₁₄ 785.87

6-Oxodocetaxel: (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[1,2b]oxet-5,6-dione 12b-acetate, 12-benzoate, 9-ester with (2R,3S)-N-tert-butoxycarbonyl-3-phenylisoserine.

C₄₃H₅₁NO₁₄ 805.86

4-Epidocetaxel: (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.

C₄₃H₅₃NO₁₄ 807.88

4-Epi-6-oxodocetaxel: (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.

C₄₃H₅₁NO₁₄ 805.86

USP Docetaxel System Suitability Mixture RS

Contains docetaxel and a small amount of 6-oxodocetaxel, O-BOC N-pyruvyl docetaxel, 4-epidocetaxel, and 4-epi-6-oxodocetaxel.