Paclitaxel Injection
» Paclitaxel Injection is a sterile, stabilized solution of Paclitaxel, suitable for dilution for intravenous administration. It contains not less than 90.0 percent and not more than 110.0 percent of the labeled amount of paclitaxel (C47H51NO14).
Packaging and storage—
Preserve in single-dose or multiple-dose containers, preferably of Type I glass, at controlled room temperature.
Labeling—
Label it to indicate that it is to be diluted with a suitable parenteral vehicle prior to intravenous infusion.
USP Reference standards 
11
—
11—
USP Endotoxin RS
USP Paclitaxel RS 
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USP Paclitaxel Related Compound B RS
10-Deacetyl-7-epipaclitaxel.
10-Deacetyl-7-epipaclitaxel.
Identification—
A:
The retention time of the major peak in the chromatogram of the Test solution corresponds to that in the chromatogram of the Standard solution, as obtained in the test for Limit of degradation products.
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.
Bacterial endotoxins 85—
It contains not more than 0.67 USP Endotoxin Unit per mg of paclitaxel.
85—
It contains not more than 0.67 USP Endotoxin Unit per mg of paclitaxel.
pH 791:
between 3.0 and 7.0, in a solution (1 in 10).
791:
between 3.0 and 7.0, in a solution (1 in 10).
Limit of degradation products—
Solution A—
Prepare 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).
621).
Standard solution—
Dissolve accurately weighed quantities of USP Paclitaxel RS and USP Paclitaxel Related Compound B RS in acetonitrile, and dilute quantitatively, and stepwise if necessary, to obtain solutions having known concentrations of about 1.2 mg per mL and 0.006 mg per mL, respectively.
Test solution—
Quantitatively dilute an accurately measured volume of Injection with acetonitrile to obtain a solution containing about 1.2 mg of paclitaxel per mL, 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.
Chromatograph the Standard solution, and record the peak responses as directed for Procedure: the resolution, R, between paclitaxel related compound B and paclitaxel is not less than 1.2; and the relative standard deviation for replicate injections is not more than 2.0%.
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.
| Time (minutes) |
Solution A
(%) |
Solution B
(%) |
Elution |
|---|---|---|---|
| 0–26 | 100 | 0 | isocratic |
| 26–66 | 100®17 | 0®83 | linear gradient |
| 66–67 | 17®100 | 83®0 | linear gradient |
| 67–75 | 100 | 0 | isocratic |
Procedure—
Separately inject equal volumes (about 10 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the areas of the analyte peaks. Calculate the percentage of each degradation product in the volume of Injection taken by the formula:
100(CS / CU)(ri / rS)
in which CS is the concentration, in mg per mL, of USP Paclitaxel Related Compound B RS in the Standard solution; CU is the concentration, in mg per mL, of paclitaxel in the Test solution, based on the labeled amount of paclitaxel per mL of Injection; ri is the peak area for each degradation product obtained from the Test solution; and rS is the peak area for paclitaxel related compound B obtained from the Standard solution. In addition to not exceeding the limits stated in Table 1, not more than 0.1% of any other paclitaxel degradation product is found; and not more than 2.0% of total paclitaxel degradation products is found.
Table 1.
| Relative Retention Time |
Name | Limit (%) |
|---|---|---|
| 0.19 | Baccatin III | 0.8 |
| 0.21 | Ethyl ester side chain | 0.4 |
| 0.50 | 10-Deacetylpaclitaxel | 0.8 |
| 0.95 | 10-Deacetyl-7-epipaclitaxel (paclitaxel related compound B) | 0.5 |
| 1.40 | 7-Epipaclitaxel | 0.6 |
Other requirements—
It meets the requirements under Injections 1.
1.
Assay—
Diluent—
Transfer 200 µL of glacial acetic acid to a 1-liter volumetric flask containing about 500 mL of methanol, mix, and dilute with methanol to volume.
Mobile phase—
Prepare a filtered and degassed mixture of water and acetonitrile (11:9). Make adjustments if necessary (see System Suitability under Chromatography 621).
621).
Standard preparation—
Dissolve an accurately weighed quantity of USP Paclitaxel RS in Diluent to obtain a solution having a known concentration of about 0.6 mg per mL.
Assay preparation—
Quantitatively dilute an accurately measured volume of Injection with Diluent to obtain a solution containing about 0.6 mg of paclitaxel per mL.
Chromatographic system (see Chromatography 621)—
The liquid chromatograph is equipped with a 227-nm detector and a 4.0-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 retention time of the paclitaxel peak is between 6.0 and 10.0 minutes; and the relative standard deviation for replicate injections is not more than 1.5%.
621)—
The liquid chromatograph is equipped with a 227-nm detector and a 4.0-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 retention time of the paclitaxel peak is between 6.0 and 10.0 minutes; 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 responses for the paclitaxel peaks. Calculate the quantity, in mg, of paclitaxel (C47H51NO14) in each mL of the Injection taken by the formula:
(L/D)C(rU / rS)
in which L is the labeled quantity, in mg, of paclitaxel in each mL of Injection; D is the concentration, in mg per mL, of paclitaxel in the Assay preparation, based on the labeled quantity; C is the concentration, in mg per mL, of USP Paclitaxel RS in the Standard preparation; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.
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 |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
|
| 85 |
Radhakrishna S Tirumalai, Ph.D.
Principal Scientific Liaison 1-301-816-8339 |
(GCM2010) General Chapters - Microbiology |
USP35–NF30 Page 4197
Pharmacopeial Forum: Volume No. 28(4) Page 1172