Dimenhydrinate Injection
»Dimenhydrinate Injection is a solution of Dimenhydrinate in a mixture of Propylene Glycol and water.It contains not less than 95.0percent and not more than 105.0percent of the labeled amount of dimenhydrinate (C17H21NO·C7H7ClN4O2).
Packaging and storage— Preserve in single-dose or in multiple-dose containers,preferably of Type Ior Type IIIglass.
Identification— Pipet 5mLof Injection into a 250-mLseparator containing 35mLof water.Add 3mLof 6Nammonium hydroxide and 10g of sodium chloride,shake the mixture until the sodium chloride dissolves,and extract with three successive 50-mLportions of ether.Wash the combined ether extracts with successive 25-mLportions of water until any color produced in the final washing by the addition of 2drops of phenolphthalein TSis discharged by 1drop of dilute hydrochloric acid (1in 100).Extract with 10mLof water containing 0.5mLof 3Nhydrochloric acid,and aerate to remove residual ether:the aqueous extract so obtained meets the requirements under Identification—Organic Nitrogenous Bases á181ñ,USP Diphenhydramine Hydrochloride RSbeing used as the reference material.
pHá791ñ: between 6.4and 7.2.
Content of 8-chlorotheophylline—
Mobile phase— Dissolve 0.81g of dl-10-camphorsulfonic acid and 0.70g of sodium acetate in 700mLof water.Add 300mLof 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 RSin methanol to obtain a Standard stock solution having a known concentration of about 0.5mg per mL.Retain a portion of this Standard stock solution for use in the Assay.Pipet 5mLinto a 50-mLvolumetric 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 50mg of dimenhydrinate,to a 100-mLvolumetric 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 5mLof this stock solution into a 50-mLvolumetric flask,dilute with methanol to volume,mix,and pass through a membrane filter having a 0.5-µm or finer porosity.
Chromatographic system(seeChromatography á621ñ)— 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 2mLper 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 10µL)of the Standard solutionand the Test solutioninto the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the quantity,in mg,of 8-chlorotheophylline (C7H7ClN4O2)in each mLof the Injection taken by the formula:
(214.61/469.96)(1000C/V)(rU/rS),
in which 214.61and 469.96are the molecular weights of 8-chlorotheophylline and dimenhydrinate,respectively;Cis the concentration,in mg per mL,of USP Dimenhydrinate RSin the Standard solution;Vis the volume,in mL,of Injection taken;and rUand rSare the peak responses obtained from the Test solutionand 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 Assayis found.
Other requirements— It meets the requirements under Injections á1ñ.
Assay—
Solution A,Solution B,Mobile phase,Internal standard solution,and Chromatographic system— Prepare as directed in the Assayunder Dimenhydrinate Tablets.
Standard preparation— Use a portion of the Standard stock solution that was prepared for the Standard solutionin the test for Content of 8-chlorotheophylline.Mix 5.0mLof this Standard stock solution and 5.0mLof 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 solutionin the test for Content of 8-chlorotheophylline.Mix 5.0mLof this stock solution and 5.0mLof Internal standard solution,and pass through a membrane filter having a 0.5-µm or finer porosity.
Procedure— Proceed as directed for Procedurein the Assayunder Dimenhydrinate Tablets.Calculate the quantity,in mg,of dimenhydrinate (C17H21NO·C7H7ClN4O2)in each mLof the Injection taken by the formula:
(200C/V)(RU/RS),
in whichCis the concentration of USP Dimenhydrinate RSin the Standard preparation;Vis the volume,in mL,of Injection taken;and the other terms are as defined therein.
Auxiliary Information— Staff Liaison:Elena Gonikberg,Ph.D.,Scientist
Expert Committee:(PA4)Pharmaceutical Analysis 4
USP28–NF23Page 659
Pharmacopeial Forum:Volume No.28(3)Page 752
Phone Number:1-301-816-8251