Doxepin Hydrochloride Oral Solution
» Doxepin Hydrochloride Oral Solution contains not less than 90.0 percent and not more than 110.0 percent of the labeled amount of doxepin (C19H21NO).
Packaging and storage Preserve in tight, light-resistant containers.
Labeling Label it to indicate that each dose is to be diluted with water or other suitable fluid to approximately 120 mL, just prior to administration.
Mobile phase Add 0.2 mL of diethylamine to a solution containing 250 mL of chloroform and 750 mL of acetonitrile in a vacuum flask. Prior to use, degas the contents of the flask by stirring vigorously with a magnetic stirrer, while applying vacuum, for 10 minutes.
Procedure Transfer 5.0 mL of the Oral Solution to a 60-mL separator, add 1 mL of sodium hydroxide solution (1 in 25), 1 g of sodium chloride, and 5.0 mL of ethyl acetate, and shake the mixture vigorously for 1 minute. Allow the phases to separate, transfer 1.0 mL of the clear upper phase to a 25-mL volumetric flask, dilute with Mobile phase to volume, and mix. Transfer about 22 mg of USP Doxepin Hydrochloride RS to a 50-mL volumetric flask, dilute with Mobile phase to volume, and mix. Inject 4-µL portions of both solutions into a high-pressure liquid chromatograph (see Chromatography 621) fitted with a 50-cm × 2-mm column packed with silica microspheres and equipped with an UV detector capable of monitoring absorption at 254 nm and a suitable recorder. Adjust the operating parameters to obtain a flow rate of about 24 mL per hour. The chromatogram of the test solution exhibits two peaks having retention times that are identical with those obtained with the Standard solution.
Uniformity of dosage units 905
for oral solution packaged in single-unit containers:meets the requirements.
Deliverable volume 698
for oral solution packaged in multiple-unit containers: meets the requirements.
pH 791: between 4.0 and 7.0, the test specimen being allowed to remain in contact with the electrodes for 15 minutes prior to the measurement.
Assay Transfer an accurately measured volume of Oral Solution, equivalent to 100 mg of doxepin, to a 100-mL volumetric flask, dilute with dilute hydrochloric acid (1 in 120) to volume, and mix. Dilute 4.0 mL of this solution with the same solvent to 50.0 mL. Transfer 15.0 mL of the resulting solution to a 125-mL separator, and extract with two 20-mL portions of ether. Dilute 10.0 mL of the extracted aqueous phase with dilute hydrochloric acid (1 in 120) to 25.0 mL. Prepare a Standard solution from a suitable quantity of USP Doxepin Hydrochloride RS, by quantitative and stepwise dilution with dilute hydrochloric acid (1 in 120) to obtain a solution having a known concentration of about 1.1 mg per mL. Take a 4-mL aliquot of the Standard solution through the above-described procedure, beginning with Dilute 4.0 mL of this solution. Concomitantly determine the absorbances of both solutions in 1-cm cells at the wavelength of maximum absorbance at about 292 nm, with a suitable spectrophotometer, using dilute hydrochloric acid (1 in 120) as the blank. Calculate the quantity, in mg, of doxepin (C19H21NO) in each mL of the Oral Solution taken by the formula:
0.885(0.1C/V)(AU / AS)in which 0.885 is the ratio of the molecular weight of doxepin to that of doxepin hydrochloride; C is the concentration, in µg per mL, of USP Doxepin Hydrochloride RS in the Standard solution; V is the volume, in mL, of Oral Solution taken; and AU and AS are the absorbances of the solution from the Oral Solution and the Standard solution, respectively.
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USP32NF27 Page 2208Pharmacopeial Forum: Volume No. 29(6) Page 1875