Identification—
Pipet 5 mL of Injection into a 250-mL separator containing 35 mL of water. Add 3 mL of 6 N ammonium hydroxide and 10 g of sodium chloride, shake the mixture until the sodium chloride dissolves, and extract with three successive 50-mL portions of ether. Wash the combined ether extracts with successive 25-mL portions of water until any color produced in the final washing by the addition of 2 drops of phenolphthalein TS is discharged by 1 drop of dilute hydrochloric acid (1 in 100). Extract with 10 mL of water containing 0.5 mL of 3 N hydrochloric acid, and aerate to remove residual ether: the aqueous extract so obtained meets the requirements under
Identification—Organic Nitrogenous Bases 
181
,
USP Diphenhydramine Hydrochloride RS being used as the reference material.
Content of 8-chlorotheophylline—
Mobile phase—
Dissolve 0.81 g of dl-10-camphorsulfonic acid and 0.70 g of sodium acetate in 700 mL of water. Add 300 mL of methanol, mix, and pass through a membrane filter having a 0.5-µm or finer porosity.
Standard solution—
Dissolve an accurately weighed quantity of
USP Dimenhydrinate RS in methanol to obtain a Standard stock solution having a known concentration of about 0.5 mg per mL. Retain a portion of this Standard stock solution for use in the
Assay. Pipet 5 mL into a 50-mL volumetric flask, dilute with methanol to volume, mix, and pass through a membrane filter having a 0.5-µm or finer porosity.
Test solution—
Transfer an accurately measured volume of Injection, equivalent to about 50 mg of dimenhydrinate, to a 100-mL volumetric flask, dilute with methanol to volume, and mix to obtain a stock solution. Retain a portion of this stock solution for use in the Assay. Pipet 5 mL of this stock solution into a 50-mL volumetric flask, dilute with methanol to volume, mix, and pass through a membrane filter having a 0.5-µm or finer porosity.
Chromatographic system (see Chromatography 621)—
The liquid chromatograph is equipped with a 280-nm detector, a 2-mm × 12.5-cm guard column that contains packing L2, and a 4.6-mm × 25-cm analytical column that contains packing L1. The flow rate is about 2 mL per minute. Chromatograph three replicate injections of the
Standard solution, and record the peak responses as directed for
Procedure: the relative standard deviation is not more than 1.0%.
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 responses for the major peaks. Calculate the quantity, in mg, of 8-chlorotheophylline (C
7H
7ClN
4O
2) in each mL of the Injection taken by the formula:
(214.61/469.96)(1000C/V)(rU / rS),
in which 214.61 and 469.96 are the molecular weights of 8-chlorotheophylline and dimenhydrinate, respectively;
C is the concentration, in mg per mL, of
USP Dimenhydrinate RS in the
Standard solution; V is the volume, in mL, of Injection taken; and
rU and
rS are the peak responses 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.
Assay—
Solution A, Solution B, Mobile phase, Internal standard solution, and Chromatographic system—
Prepare as directed in the
Assay under
Dimenhydrinate Tablets.
Standard preparation—
Use a portion of the Standard stock solution that was prepared for the Standard solution in the test for Content of 8-chlorotheophylline. Mix 5.0 mL of this Standard stock solution and 5.0 mL of Internal standard solution, and pass through a membrane filter having a 0.5-µm or finer porosity.
Assay preparation—
Use a portion of the stock solution that was prepared for the Test solution in the test for Content of 8-chlorotheophylline. Mix 5.0 mL of this stock solution and 5.0 mL of Internal standard solution, and pass through a membrane filter having a 0.5-µm or finer porosity.
Procedure—
Proceed as directed for
Procedure in the
Assay under
Dimenhydrinate Tablets. Calculate the quantity, in mg, of dimenhydrinate (C
17H
21NO·C
7H
7ClN
4O
2) in each mL of the Injection taken by the formula:
(200C / V)(RU / RS),
in which
C is the concentration of
USP Dimenhydrinate RS in the
Standard preparation; V is the volume, in mL, of Injection taken; and the other terms are as defined therein.
