Add the following:
Docetaxel Injection
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.
IDENTIFICATION
• A. Thin-Layer Chromotographic Identification Test 
201
201
Standard solution:
0.4 mg/mL of USP Docetaxel RS in methylene chloride containing 1% (v/v) of polysorbate 80
Sample solution:
0.4 mg/mL of docetaxel (anhydrous) in methylene chloride, from Injection
Adsorbent:
0.25-mm layer of chromatographic silica gel mixture containing a fluorescent indicator
Developing solvent system:
Methylene chloride and methanol (23:2)
TLC tank:
Lined with filter paper
Analysis:
After removing the plate from the tank, allow to dry in a fume hood, and view under UV light at 254 nm.
Acceptance criteria:
Meets the requirements
• B.
The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
ASSAY
• Procedure
Solution A:
Water
Solution B:
Acetonitrile
Mobile phase:
See Table 1.
Table 1
| Time (min) |
Solution A (%) |
Solution B (%) |
|---|---|---|
| 0 | 72 | 28 |
| 9.0 | 72 | 28 |
| 39.0 | 28 | 72 |
| 39.1 | 0 | 100 |
| 49.0 | 0 | 100 |
| 49.1 | 72 | 28 |
| 60 | 72 | 28 |
Diluent:
Acetonitrile, 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 the 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 the 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
Mode:
LC
Detector:
UV 232 nm
Refrigerated autosampler temperature:
10
Column:
4.6-mm × 15-cm; 3.5-µm packing L1
Column temperature:
45
Flow rate:
1.2 mL/min
Injection size:
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 = (rU/rS) × (CS/CU) × 100
| rU | = | = peak area from the Sample solution |
| rS | = | = peak area from the Standard solution |
| CS | = | = concentration of USP Docetaxel RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of docetaxel (anhydrous) in the Sample solution (mg/mL) |
Acceptance criteria:
90.0%–110.0%
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
Signal-to-noise ratio:
NLT 10 for the docetaxel peak, Sensitivity solution
Relative standard deviation:
NMT 1.0%, Standard solution
Analysis
Sample:
Sample solution
Calculate the percentage of each impurity in the portion of Injection taken:
Result = (rU/rT) × (1/F) × 100
| rU | = | = peak area of each individual impurity from the Sample solution |
| rT | = | = sum of all of the peak areas from the Sample solution |
| F | = | = relative response factor for each individual impurity (see Table 2) |
Acceptance criteria
Individual impurities:
See Table 2. [Note—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
| Name | Relative Retention Time |
Relative Response Factor |
Acceptance Criteria, NMT (%) |
|---|---|---|---|
| 10-Deacetyl baccatina |
0.27 | 1.5 | 0.30 |
| 2-Debenzoxyl 2-pentenoyl docetaxelb | 0.97 | — | — |
| Docetaxel | 1.00 | — | — |
| Crotonaldehyde analogc |
1.05 | 1.0 | 1.3 |
| 6-Oxodocetaxeld | 1.08 | 1.0 | 1.5 |
| 4-Epidocetaxele | 1.13 | 1.0 | 0.5 |
| 4-Epi-6- oxodocetaxelf |
1.18 | 1.0 | 0.5 |
| Any unspecified impurity |
— | 1.0 | 0.2 |
| Total impurities | — | — | 3.5 |
|
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 (2b,5b,7b,10b,13a)-4-acetoxy-13-(((2R,3S)- 3-[(tert-butoxycarbonyl)amino]-2-hydroxy-3- phenylpropanoyl)oxy)-1,7,10-trihydroxy-9-oxo-5,20-epoxytax-11-en-2-yl (2E)-2- methylbut-2-enoate.
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 (2b,5b,7a,10b,13a)-4-acetoxy-13-(((2R,3S)- 3-[(tert-butoxycarbonyl)amino]-2-hydroxy-3- phenylpropanoyl)oxy)-1,7,10-trihydroxy-9-oxo-5,20-epoxytax-11-en-2-yl benzoate.
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 (2b,5b,7a,10b,13a)-4-acetoxy-13-(((2R,3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-3- phenylpropanoyl)oxy)-1,7,10-trihydroxy-9-oxo-5,20-epoxytax-11-en-2-yl benzoate.
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 (2b,5b,7a,13a)- 4-acetoxy-13-(((2R,3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-3- phenylpropanoyl)oxy)-1,7-dihydroxy-9,10-dioxo-5,20-epoxytax-11-en-2-yl benzoate.
|
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SPECIFIC TESTS
• Bacterial Endotoxins Test 85:
It contains NMT 1.94 USP Endotoxin Units/mg of docetaxel (anhydrous).
85:
It contains NMT 1.94 USP Endotoxin Units/mg of docetaxel (anhydrous).
• Sterility Tests 71:
It meets the requirements when tested as directed in the Test for Sterility of the Product to Be Examined, Membrane Filtration.
71:
It meets the requirements when tested as directed in the Test for Sterility of the Product to Be Examined, Membrane Filtration.
• Particulate Matter in Injections 788:
Meets the requirements for small-volume injections
788:
Meets the requirements for small-volume injections
• Other Requirements:
Meets the requirements in Injections 1
1
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
11
USP Docetaxel RS 
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USP Docetaxel Identification RS
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[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. ]
USP Endotoxin RS
USP35
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Feiwen Mao, M.S.
Senior Scientific Liaison 1-301-816-8320 |
(SM32010) Monographs - Small Molecules 3 |
| 85 |
Radhakrishna S Tirumalai, Ph.D.
Principal Scientific Liaison 1-301-816-8339 |
(GCM2010) General Chapters - Microbiology |
| 71 |
Radhakrishna S Tirumalai, Ph.D.
Principal Scientific Liaison 1-301-816-8339 |
(GCM2010) General Chapters - Microbiology |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 2954
Pharmacopeial Forum: Volume No. 37(1)