Paclitaxel
C47H51NO14
853.91
Benzenepropanoic acid, -(benzoylamino)--hydroxy-, 6,12b-bis(acetyloxy)-12-(benzoyloxy)-2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-4,11-dihydroxy-4a,8,13,13-tetramethyl-5-oxo-7,11-methano-1H-cyclodeca[3,4]benz[1,2-b]oxet-9-yl ester, [2aR-[2a,4,4a,6,9(R*,S*),11,12,12a,12b]]-. (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 6,12b-diacetate, 12-benzoate, 9-ester with (2R,3S)-N-benzoyl-3-phenylisoserine [33069-62-4]. » Paclitaxel contains not less than 97.0 percent and not more than 102.0 percent of C47H51NO14, calculated on the anhydrous, solvent-free basis.
CautionPaclitaxel is cytotoxic. Great care should be taken to prevent inhaling particles of Paclitaxel and exposing the skin to it.
Packaging and storage
Preserve in tight, light-resistant containers, and store at controlled room temperature.
Labeling
The labeling indicates the type of process used to produce the material and the Related compounds test with which the material complies.
USP Reference standards 11
USP Endotoxin RS. USP Paclitaxel RS . USP Paclitaxel Related Compound A RS . USP Paclitaxel Related Compound B RS . USP Paclitaxel Impurity Mixture RS.
Identification
B:
The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.
Specific rotation 781S:
between 49.0 and 55.0 at 20, calculated on the anhydrous, solvent-free basis.
Test solution:
10 mg per mL, in methanol.
Microbial enumeration tests 61 and Tests for specified microorganisms 62
The total aerobic microbial count does not exceed 100 cfu per g. It meets the requirements of the tests for the absence of Staphylococcus aureus, Pseudomonas aeruginosa, Salmonella species, and Escherichia coli.
Bacterial endotoxins 85
It contains not more than 0.4 USP Endotoxin Unit per mg of paclitaxel.
Water, Method Ic 921:
not more than 4.0%.
Residue on ignition 281:
not more than 0.2%.
Heavy metals, Method II 231:
0.002%.
Related compounds
test 1 (for material labeled as isolated from natural sources)
If the material complies with this test, the labeling indicates that it meets USP Related compounds Test 1.
Diluent
Prepare as directed in the Assay.
Solution A
Prepare filtered and degassed acetonitrile.
Solution B
Prepare filtered and degassed water.
Mobile phase
Use variable mixtures of Solution A and Solution B as directed for Chromatographic system. Make adjustments if necessary (see System Suitability under Chromatography 621).
System suitability solution
Dissolve accurately weighed quantities of USP Paclitaxel Related Compound A RS and USP Paclitaxel Related Compound B RS in methanol to obtain a solution having known concentrations of about 10 µg of each per mL. Transfer 5.0 mL of this solution to a 50-mL volumetric flask, dilute with Diluent to volume, and mix.
Standard solution
Dissolve, with the aid of sonication, an accurately weighed quantity of USP Paclitaxel RS in Diluent, and dilute quantitatively, and stepwise if necessary, with Diluent to obtain a solution having a known concentration of about 5 µg per mL.
Test solution
Use the Assay preparation.
Chromatographic system (see Chromatography 621)
The liquid chromatograph is equipped with a 227-nm detector and a 4.6-mm × 25-cm column that contains 5-µm packing L43. The flow rate is about 2.6 mL per minute. The column temperature is maintained at 30. The chromatograph is programmed as follows.
Procedure
Inject a volume (about 15 µL) of the Test solution into the chromatograph, record the chromatogram, and measure the areas for the major peaks. Calculate the percentage of each impurity in the portion of Paclitaxel taken by the formula:
100(Fri / rU)
in which F is the relative response factor for each impurity peak (see Table 1 for values); ri is the peak area for each individual impurity; and rU is the peak area for paclitaxel.
Table 1
test 2 (for material labeled as produced by a semisynthetic process)
If the material complies with this test, the labeling indicates that it meets USP Related compounds Test 2.
Diluent
Use acetonitrile.
Solution A
Use a filtered and degassed mixture of water and acetonitrile (3:2).
Solution B
Use filtered and degassed acetonitrile.
Mobile phase
Use variable mixtures of Solution A and Solution B as directed for Chromatographic system. Make adjustments if necessary (see System Suitability under Chromatography 621).
System suitability solution
Dissolve accurately weighed quantities of USP Paclitaxel RS and USP Paclitaxel Related Compound B RS in Diluent, shaking and sonicating if necessary, to obtain a solution having known concentrations of about 0.96 mg and 0.008 mg per mL, respectively.
Test solution
Transfer about 10 mg of Paclitaxel, accurately weighed, to a 10-mL volumetric flask, dissolve in and dilute with Diluent to volume, shaking and sonicating if necessary, and mix.
Chromatographic system (see Chromatography 621)
The liquid chromatograph is equipped with a 227-nm detector and a 4.6-mm × 15-cm column that contains 3-µm packing L1. The flow rate is about 1.2 mL per minute. The column temperature is maintained at 35. The chromatograph is programmed as follows.
Procedure
Separately inject equal volumes (about 15 µL) of the Diluent and the Test solution into the chromatograph, record the chromatograms, and measure the areas for all the peaks. Disregard any peaks due to the Diluent. Calculate the percentage of each impurity in the portion of Paclitaxel taken by the formula:
100(Fri / rs)
in which F is the relative response factor for each impurity (see Table 2 for values); ri is the peak area for each impurity obtained from the Test solution; and rs is the sum of the areas of all the peaks obtained from the Test solution.
Table 2
test 3 (for material labeled as produced by a plant cell fermentation process)
If the material complies with this test, the labeling indicates that it meets USP Related compounds Test 3.
Solution A
Prepare a filtered and degassed mixture of water and acetonitrile (3:2).
Solution B
Prepare filtered and degassed acetonitrile.
Mobile phase
Use variable mixtures of Solution A and Solution B as directed for Chromatographic system. Make adjustments if necessary (see System Suitability under Chromatography 621).
System suitability solution
Dissolve USP Paclitaxel Impurity Mixture RS in acetonitrile, sonicating if necessary, to obtain a solution having a known concentration of about 1 mg per mL.
Standard solution
Dissolve an accurately weighed quantity of USP Paclitaxel RS in acetonitrile, sonicating if necessary, to obtain a solution having a known concentration of about 1 mg per mL.
Test solution
Transfer about 10 mg of Paclitaxel, accurately weighed, to a 10-mL volumetric flask. Dissolve in and dilute with acetonitrile to volume, sonicating if necessary, and mix.
Chromatographic system (see Chromatography 621)
The liquid chromatograph is equipped with a 227-nm detector and a 4.6-mm × 15-cm column that contains 3-µm packing L1. The flow rate is about 1.2 mL per minute. The chromatograph is programmed as follows.
Table 3
Procedure
Inject a volume (about 12 µL) of the Test solution into the chromatograph, record the chromatogram, and measure the areas for all the peaks. Calculate the percentage of each impurity in the portion of Paclitaxel taken by the formula:
100(ri / rU)
in which ri is the response of each individual impurity; and rU is the sum of the areas of all the peaks obtained from the Test solution. In addition to not exceeding the limits for paclitaxel related impurities in Table 3, not more than 0.1% of any other single impurity is found; and not more than 2.0% of total impurities is found.
Assay
Diluent
Prepare a mixture of methanol and acetic acid (200:1).
Mobile phase
Prepare a filtered and degassed mixture of water and acetonitrile (11:9). Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard preparation
Dissolve, using sonication if necessary, an accurately weighed quantity of USP Paclitaxel RS in Diluent, and dilute quantitatively, and stepwise if necessary, with Diluent to obtain a solution having a known concentration of about 1 mg per mL.
Assay preparation
Transfer about 10 mg of Paclitaxel, accurately weighed, to a 10-mL volumetric flask. Dissolve in Diluent, using sonication if necessary, dilute with Diluent to volume, and mix.
Chromatographic system (see Chromatography 621)
The liquid chromatograph is equipped with a 227-nm detector and a 4.6-mm × 25-cm column that contains 5-µm packing L43. The flow rate is about 1.5 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the tailing factor is between 0.7 and 1.3; and the relative standard deviation for replicate injections is not more than 1.5%.
Procedure
Separately inject equal volumes (about 10 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the areas for the major peaks. Calculate the quantity, in mg, of C47H51NO14 in the portion of Paclitaxel taken by the formula:
10C(rU / rS)
in which C is the concentration, in mg per mL, of USP Paclitaxel RS in the Standard preparation; and rU and rS are the peak responses for paclitaxel obtained from the Assay preparation and the Standard preparation, respectively.
Auxiliary Information
Please check for your question in the FAQs before contacting USP.
Chromatographic Column
USP32NF27 Page 3187
Pharmacopeial Forum: Volume No. 33(2) Page 250
Chromatographic columns text is not derived from, and not part of, USP 32 or NF 27.
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