Medium: water; 900 mL.

Apparatus 2: 50 rpm.

Time: 45 minutes.

Procedure— Determine the amount of C17H21NO·C7H7ClN4O2 dissolved by employing UV absorption at the wavelength of maximum absorbance at about 276 nm on filtered portions of the solution under test, suitably diluted with Dissolution Medium, if necessary, in comparison with a Standard solution having a known concentration of USP Dimenhydrinate RS in the same Medium.

Tolerances— Not less than 75% (Q) of the labeled amount of C17H21NO·C7H7ClN4O2 is dissolved in 45 minutes.

Ammonium bicarbonate solution, Diluent, Solution A, Solution B, Mobile phase, Internal standard solution, and Chromatographic system— Prepare as directed in the Assay.

Standard solution— Prepare as directed for Standard preparation in the Assay.

Test solution— Prepare as directed for Assay preparation in the Assay.

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 for the major peaks. Calculate the quantity, in mg, of 8-chlorotheophylline (C7H7ClN4O2) per Tablet taken by the formula: in which 214.61 and 469.96 are the molecular weights of 8-chlorotheophylline and dimenhydrinate, respectively; W is the weight, in mg, of USP Dimenhydrinate RS in the Standard solution; and RU and RS are peak area ratios of 8-chlorotheophylline to the internal standard obtained from the Test solution and the Standard solution, respectively. An amount of 8-chlorotheophylline that is between 43.4% and 47.9% of the amount of dimenhydrinate obtained in the Assay is found.

(Official January 1, 2007)

Ammonium bicarbonate solution— Dissolve 4 g of ammonium bicarbonate in 250 mL of water.

Diluent— Dissolve 4 g of ammonium bicarbonate in 200 mL of water. Add 50 mL of methanol, and mix.

Solution A— Dissolve 0.8 g of ammonium bicarbonate in 800 mL of water. Add 200 mL of methanol, filter, and degas.

Solution B— Dissolve 0.8 g of ammonium bicarbonate in 150 mL of water. Add 850 mL of methanol, filter, and degas.

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).

Internal standard solution— Prepare a solution in methanol containing 2.0 mg of 2-hydroxybenzyl alcohol per mL.

Standard preparation— Accurately weigh about 50 mg of USP Dimenhydrinate RS, add about 5 mL of Ammonium bicarbonate solution and 20.0 mL of Internal standard solution, and mix. To 1 mL of this solution add about 9 mL of Diluent, and mix.

Assay preparation— Transfer 5 Tablets into a 250-mL volumetric flask, add 25 mL of Ammonium bicarbonate solution, and shake gently to disperse, sonicating if necessary. Add 100.0 mL of Internal standard solution, shake vigorously for 30 minutes, and centrifuge. To 1 mL of the clear supernatant add about 9 mL of Diluent, and mix.

Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 229-nm detector and a 4.6-mm × 25-cm column that contains packing L7. The flow rate is about 1.5 mL per minute. The chromatograph is programmed as follows. Chromatograph the Standard preparation, and record the peak areas as directed for Procedure: the relative retention times are about 0.3 for 8-chlorotheophylline, 0.5 for the internal standard, and 1.0 for diphenhydramine; the resolution, R, between 8-chlorotheophylline and the internal standard is not less than 4.5; and the relative standard deviation for replicate injections is not more than 2.0%.

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 areas for the major peaks. Calculate the quantity, in mg, of dimenhydrinate (C17H21NO·C7H7ClN4O2) per Tablet taken by the formula: in which W is the weight, in mg, of USP Dimenhydrinate RS in the Standard preparation; and RU and RS are the peak area ratios of diphenhydramine to the internal standard obtained from the Assay preparation and the Standard preparation, respectively.