Completeness and clarity of solution—
Separately prepare a 1 in 10 solution of it in water and 1 in 10 solution of it in chloroform: each solution is practically clear and shows not more than a light yellow color.
NOTE—Throughout the following procedures, protect test or assay specimens, the Reference Standard, and solutions containing them, by conducting the procedures without delay, under subdued light, or using low-actinic glassware.
Related substances—
Standard preparation
and
Standard dilutions—Dissolve an accurately weighed quantity of
USP Promethazine Hydrochloride RS in methylene chloride to obtain a solution containing 10.0 mg per mL (
Standard preparation). Prepare a series of quantitative dilutions of the
Standard preparation in methylene chloride to contain 0.2, 0.1, 0.05, and 0.025 mg per mL (
Standard dilutions) corresponding to 2.0%, 1.0%, 0.5%, and 0.25% of impurities, respectively.
Test solution—
Dissolve 100 mg, accurately weighed, of Promethazine Hydrochloride in 10.0 mL of methylene chloride.
Procedure—
Using a 20- × 20-cm thin-layer chromatographic plate (see
Chromatography 
621
) coated with a 0.25-mm layer of silica gel mixture, apply 10-µL portions of the
Test preparation, the
Standard preparation, and each of the
Standard dilutions 2.5 cm from the lower edge of the plate. Develop the plate in an unsaturated tank containing a mixture of ethyl acetate, acetone, alcohol, and ammonium hydroxide (90:45:2:1). After the solvent has moved not less than 10 cm, air-dry the plate, and view under short-wavelength UV light: the
RF value of the principal spot obtained from the
Test preparation corresponds to that from the
Standard preparation. Estimate the concentration of any other spots observed in the lane for the
Test preparation by comparison with the
Standard dilutions: the sum of the impurities is not greater than 2.0%, and no single impurity is greater than 1.0%.
Assay—
Dissolve about 700 mg of Promethazine Hydrochloride, accurately weighed, in a mixture of 75 mL of glacial acetic acid and 10 mL of
mercuric acetate TS. Add 1 drop of
crystal violet TS, and titrate with 0.1 N perchloric acid VS to a blue endpoint. Perform a blank determination, and make any necessary correction. Each mL of 0.1 N perchloric acid is equivalent to 32.09 mg of C
17H
20N
2S·HCl.
;)
-trimethyl-, monohydrochloride, (±)-.
for 4 hours: it loses not more than 0.5% of its weight.