Clindamycin Phosphate Vaginal Inserts

» Clindamycin Phosphate Vaginal Inserts contain the equivalent of not less than 90.0 percent and not more than 110.0 percent of the labeled amount of clindamycin (C18H33ClN2O5S).

Packaging and storage— Preserve in well-closed containers, at controlled room temperature or in a cool place.

—

USP Clindamycin Hydrochloride RS

USP Clindamycin Phosphate RS

Identification—

A: Infrared Absorption

197M

—

Procedure— Transfer a Vaginal Insert into a suitable container, add 120 mL of methylene chloride, insert a stopper, and shake until the Vaginal Insert is completely dissolved. Using a vacuum, pass through a methylene chloride-compatible filter having a 0.45-µm porosity. Rinse the filter with several portions of methylene chloride, and allow the filter to air-dry. The IR absorption of the white residue from the filter exhibits maxima at the same wavelengths as that of a similar preparation of USP Clindamycin Phosphate RS.

B: The retention time of the clindamycin phosphate peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.

Uniformity of dosage units

905

: meet the requirements.

Assay—

Mobile phase— Dissolve 10.54 g of monobasic potassium phosphate in 775 mL of water, and adjust with phosphoric acid to a pH of 2.5. Add 225 mL of acetonitrile, and mix. Pass through a filter having a 0.45-µm or finer porosity, and degas. Make adjustments if necessary (see System Suitability under Chromatography

625

pH 2.5 Buffer— Dissolve 10.54 g of monobasic potassium phosphate in 1000 mL of water, and adjust with phosphoric acid to a pH of 2.5.

Resolution solution— Prepare a solution in pH 2.5 Buffer containing in each mL about 0.24 mg of USP Clindamycin Phosphate RS and about 6 µg of USP Clindamycin Hydrochloride RS.

Standard preparation— Dissolve an accurately weighed quantity of USP Clindamycin Phosphate RS in pH 2.5 Buffer to obtain a solution having a known concentration of about 0.24 mg per mL.

Assay preparation— Transfer one Vaginal Insert to a suitable 100-mL container. Add 40 mL of isooctane, and seal the container tightly with a teflon-lined septum and crimp cap. Shake vigorously for about 15 minutes until all of the Vaginal Insert is dissolved. Add 40.0 mL of pH 2.5 Buffer. Recap the container tightly, and shake vigorously for not less than 30 minutes, taking care to avoid leakage. Allow the layers to separate, and remove a volume of the lower aqueous layer sufficient to perform the following steps. Pass the aqueous solution through a filter having a 5-µm or finer porosity, discarding the first 2 mL of the filtrate. Collect the remaining filtrate, and dilute a portion quantitatively, and stepwise if necessary, with pH 2.5 Buffer to obtain a solution containing the equivalent of about 0.2 mg of clindamycin (C18H33ClN2O5S) per mL, and mix.

Chromatographic system (see Chromatography

621

)— The liquid chromatograph is equipped with a 210-nm detector and a 4.6-mm × 25-cm column that contains packing L7. The flow rate is about 1 mL per minute. Chromatograph the Resolution solution as directed for Procedure. The resolution, R, between clindamycin phosphate and clindamycin hydrochloride is not less than 2.0, when calculated by the formula:

1.177[(t2 – t1) / (wh1 + wh2)]

in which t2 is the retention time, in minutes, of clindamycin hydrochloride; t1 is the retention time, in minutes, of clindamycin phosphate; whl is the width, in minutes, of the clindamyicn phosphate peak at half-height; and wh2 is the width, in minutes, of the clindamyicn hydrochloride peak at half-height. Chromatograph the Standard preparation as directed for Procedure: the relative standard deviation for replicate injections is not more than 2.5%.

Procedure— Separately inject equal volumes (about 35 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the major peak responses. Calculate the quantity, in mg, of clindamycin (C18H33ClN2O5S) equivalent in the Vaginal Insert taken by the formula:

(CP/1000)(L/ D)(rU / rS)

in which C is the concentration, in mg per mL, of USP Clindamycin Phosphate RS in the Standard preparation; P is the potency, in µg, of clindamycin (C18H33ClN2O5S) per mg, of USP Clindamycin Phosphate RS; L is the labeled quantity, in mg, of clindamycin (C18H33ClN2O5S) equivalent in the Vaginal Insert; D is the concentration, in mg per mL, of clindamycin equivalent in the Assay preparation, based on the labeled quantity in the Vaginal Insert and the extent of dilution; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively. Use as the Assay value the average of the determinations obtained for Content Uniformity in the test for Uniformity of dosage units.

Auxiliary Information— Please check for your question in the FAQs before contacting USP.

Topic/Question	Contact	Expert Committee
Monograph	Ahalya Wise, M.S. Senior Scientific Liaison 1-301-816-8161	(SM12010) Monographs - Small Molecules 1
Reference Standards	RS Technical Services 1-301-816-8129 rstech@usp.org

USP35–NF30 Page 2709

Pharmacopeial Forum: Volume No. 29(3) Page 620