Promethazine Hydrochloride Injection
»Promethazine Hydrochloride Injection is a sterile solution of Promethazine Hydrochloride in Water for Injection.It contains not less than 95.0percent and not more than 110.0percent of the labeled amount of C17H20N2S·HCl.
Packaging and storage— Preserve in single-dose or in multiple-dose containers,preferably of Type Iglass,protected from light.
USP Reference standards á11ñ— USP Promethazine Hydrochloride RS.USP Endotoxin RS.
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.
Identification— Add a volume of Injection,equivalent to about 50mg of promethazine hydrochloride,to 20mLof dilute hydrochloric acid (1in 1000)contained in a separator.Wash the solution with a 20-mLportion of methylene chloride,discarding the washing.Add 2mLof 1Nsodium hydroxide and 20mLof methylene chloride,and shake for 2minutes.Evaporate the methylene chloride extract on a steam bath with the aid of a stream of nitrogen to dryness.Dissolve the residue in 4mLof carbon disulfide,filter through paper,if necessary,and determine the IRabsorption spectrum as directed under Identification—Organic Nitrogenous Bases á181ñ,obtaining the spectrum of USP Promethazine Hydrochloride RSas directed:the Injection meets the requirements of the test.
Bacterial endotoxins á85ñ— It contains not more than 5.0USP Endotoxin Units per mg of promethazine hydrochloride.
pHá791ñ: between 4.0and 5.5.
Other requirements— It meets the requirements under Injections á1ñ.
Assay—
Mobile phase— Dissolve 1g of sodium 1-pentanesulfonate in 500mLof water,add 500mLof acetonitrile and 5mLof glacial acetic acid,filter,and degas.Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
Standard preparation— Dissolve an accurately weighed quantity of USP Promethazine Hydrochloride RSin Mobile phase,and dilute quantitatively,and stepwise if necessary,with the same solvent to obtain a solution having a known concentration of about 0.1mg per mL.
Assay preparation— Transfer an accurately measured volume of Injection,equivalent to about 50mg of promethazine hydrochloride,to a 50-mLvolumetric flask,dilute with Mobile phaseto volume,and mix.Transfer 10.0mLof the resulting solution to a 100-mLvolumetric flask,dilute with Mobile phaseto volume,and mix.
System suitability preparation— Dissolve a suitable quantity of phenothiazine in Standard preparationto obtain a solution containing about 10µg of phenothiazine per mL.
Chromatographic system (see Chromatography á621ñ)—The liquid chromatograph is equipped with a 254-nm detector and a 4.6-mm ×30-cm column that contains packing L11.The flow rate is about 1.5mLper minute.Chromatograph the System suitability preparation,and record the peak responses as directed for Procedure:the resolution,R,between the promethazine and phenothiazine peaks is not less than 3.0,and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure— Separately inject equal volumes (about 30µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.The relative retention times are 1.0for promethazine and about 1.6for phenothiazine.Calculate the quantity,in mg,of C17H20N2S·HCl in each mLof the Injection taken by the formula:
500(C/V)(rU/rS),
in which Cis the concentration,in mg per mL,of USP Promethazine Hydrochloride RSin the Standard preparation,Vis the volume,in mL,of Injection taken,and rUand rSare the peak responses obtained from the Assay preparationand the Standard preparation,respectively.
Auxiliary Information— Staff Liaison:Karen A Russo,Ph.D.,Scientist
Expert Committee:(PA1)Pharmaceutical Analysis 1
USP28–NF23Page 1641
Phone Number:1-301-816-8379