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Etoposide Capsules
» Etoposide Capsules contain not less than 90.0 percent and not more than 110.0 percent of the labeled amount of etoposide (C29H32O13).
Caution—Etoposide is potentially cytotoxic. Great care should be taken to prevent inhaling particles of Etoposide and exposing the skin to it.
Packaging and storage— Preserve in tight containers in a cold place. Do not freeze.
USP Reference standards 11— USP Etoposide RS. USP Etoposide Related Compound A RS.
Identification—
A:Infrared Absorption 197K—
Test specimen— Transfer a suitable quantity of the contents of Capsules, equivalent to about 100 mg of etoposide, to a separator containing 100 mL of water. Extract twice with 20-mL portions of chloroform, separate and combine the organic layer, dry over anhydrous sodium sulfate, and filter. Transfer the dried filtrate to a second separator, extract with 30 mL of water, and allow the layers to separate. Drain the chloroform layer through a bed of anhydrous sodium sulfate contained in a filter funnel into a round bottom flask, and evaporate the chloroform at a temperature of 30 ± 5 using a rotary evaporator. Dissolve the oily residue obtained in 5 mL of water, shake gently, and allow to stand for 30 minutes. Filter, collecting the precipitate formed on a glass filter funnel, wash the precipitate with three 20-mL portions of water, and allow the precipitate to dry on the filter for about 90 minutes in a vacuum oven at 40. Prepare a dispersion of the precipitate in KBr at a ratio 1 in 100.
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.
Dissolution 711—
Medium: pH 4.5 acetate buffer; 900 mL.
Apparatus 2: 50 rpm.
Time: 30 minutes.
Determine the amount of C29H32O13 dissolved by employing the following method.
Buffer solution— Dissolve 5.44 g of sodium acetate in 2000 mL of water, adjust with acetic acid to a pH of 4.0, and filter.
Mobile phase— Prepare a filtered and degassed mixture of Buffer solution and acetonitrile (74:26). Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard solution— Dissolve, with sonication, an accurately weighed quantity of USP Etoposide RS in a volume of methanol equivalent to 2% of the final solution volume. Dilute with Dissolution Medium to obtain a solution having a known concentration of about 55 µg per mL, and mix.
Test solution— At 30 minutes withdraw a 10-mL aliquot from the dissolution vessel.
Chromatographic system— The liquid chromatograph is equipped with a 240-nm detector and a 3.9-mm × 30-cm column that contains packing L11. The flow rate is about 2 mL per minute. Chromatograph the Standard solution, and record the peak responses as directed for Procedure: the relative standard deviation for replicate injections is not more than 2.0%.
Procedure— Separately inject equal volumes (about 50 µL) of the filtered portions of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Determine the amount of C29H32O13 dissolved.
Tolerances— Not less than 80% (Q) of the labeled amount of C29H32O13 is dissolved in 30 minutes.
Uniformity of dosage units 905: meet the requirements.
Related compounds— Proceed as directed in the test for Related compounds under Etoposide: not more than 2.0% of picroetoposide is found; and not more than 3.0% of total impurities is found.
Residual solvents 467: meet the requirements.
(Official January 1, 2007)
Assay—
Buffer solution, Mobile phase, Standard preparation, System suitability solution, and Chromatographic system— Proceed as directed in the Assay under Etoposide.
Assay preparation— Transfer an accurately counted number of Capsules, equivalent to about 500 mg of etoposide, to a 500-mL volumetric flask, add about 400 mL of Mobile phase, and stir using a magnetic bar for about 15 minutes, followed by sonication for about 1 hour with occasional shaking. Cool, dilute with Mobile phase to volume, stir for an additional 5 minutes, and filter. Transfer 10.0 mL of this solution to a 50-mL volumetric flask, dilute with Mobile phase to volume, and mix.
Procedure— Proceed as directed in the Assay under Etoposide. Calculate the quantity, in mg, of etoposide (C29H32O13) per Capsule by the formula:
2500(C/N)(rU / rS),
in which C is the concentration, in mg per mL, of USP Etoposide RS in the Standard preparation; N is the number of Capsules taken; and rU and rS are the etoposide peak responses obtained from the Assay preparation and the Standard preparation, respectively.
Auxiliary Information— Staff Liaison : Feiwen Mao, M.S., Senior Scientific Associate
Expert Committee : (MDOOD05) Monograph Development-Ophthalmics Oncologics and Dermatologicals
USP29–NF24 Page 878
Pharmacopeial Forum : Volume No. 27(5) Page 3004
Phone Number : 1-301-816-8320