Chlorpromazine Hydrochloride Injection
»Chlorpromazine Hydrochloride Injection is a sterile solution of Chlorpromazine Hydrochloride in Water for Injection.It contains,in each mL,not less than 23.75mg and not more than 26.25mg of C17H19ClN2S·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 Chlorpromazine 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—
A: Transfer a volume of Injection,equivalent to about 25mg of chlorpromazine hydrochloride,to a 10-mLvolumetric flask,dilute with methanol to volume,and mix (test solution).Dissolve a suitable quantity of USP Chlorpromazine Hydrochloride RSin dilute methanol (9in 10)to obtain a Standard solution having a known concentration of 2.5mg per mL.Apply separately 5-µLportions of each of the two solutions to the starting line of a thin-layer chromatographic plate (see Chromatography á621ñ)coated with chromatographic silica gel mixture.Develop the chromatogram in a solvent system consisting of a freshly prepared mixture of equal volumes of ether and ethyl acetate saturated with ammonium hydroxide until the solvent front has moved about 10cm from the origin.Remove the plate from the developing chamber,air-dry for 20minutes,then view under short-wavelength UVlight:the RFvalue of the principal spot obtained from the test solution corresponds to that obtained from the Standard solution.
B: It responds to the tests for Chloride á191ñ.
Bacterial endotoxins á85ñ— It contains not more than 6.9USP Endotoxin Units per mg of chlorpromazine hydrochloride.
pHá791ñ: between 3.4and 5.4.
Limit of chlorpromazine sulfoxide— [NOTE—Conduct this test without exposure to daylight,and with the minimum necessary exposure to artificial light.]
Test preparation— Pipet 4mLof the test solution prepared with methanol as directed in Identificationtest Ainto a 10-mLvolumetric flask,dilute with methanol to volume,and mix.
Standard preparation— Dissolve a suitable quantity of USP Chlorpromazine Hydrochloride RSin methanol to obtain a solution having a concentration of 50µg per mL.
Procedure— Apply separate 10-µLportions of the Standard preparationand the Test preparationto the starting line of a thin-layer chromatographic plate coated with a 0.25-mm layer of chromatographic silica gel mixture.Dry the applied solutions with the aid of a stream of nitrogen.Develop the chromatogram,using as the solvent system a freshly prepared mixture of equal volumes of ether and ethyl acetate saturated with ammonium hydroxide,until the solvent front has moved about 13cm from the origin.Remove the plate from the chamber,and air-dry for 30minutes.Examine under short-wavelength UVlight:the area and intensity of the only other spot in the test specimen chromatogram,other than the principal spot,are not greater than those of the spot from the Standard preparation(5.0%).
Other requirements— It meets the requirements under Injections á1ñ.
Assay— Transfer an accurately measured volume of Injection,equivalent to about 100mg of chlorpromazine hydrochloride,to a 500-mLvolumetric flask,add 0.1Nhydrochloric acid to volume,and mix.Pipet 10mLof the solution into a 250-mLseparator,add about 20mLof water,render alkaline with ammonium hydroxide,and extract with four 25-mLportions of ether.Extract the combined ether extracts with four 25-mLportions of 0.1Nhydrochloric acid,collecting the aqueous extracts in a 250-mLvolumetric flask.Aerate to remove residual ether,add 0.1Nhydrochloric acid to volume,and mix.Dissolve a suitable quantity,accurately weighed,of USP Chlorpromazine Hydrochloride RSin 0.1Nhydrochloric acid,and dilute quantitatively and stepwise with the same acid to obtain a Standard solution having a known concentration of about 8µg per mL.Concomitantly determine the absorbances of both solutions in 1-cm cells at the wavelength of maximum absorbance at about 254nm and at 277nm,with a suitable spectrophotometer,using 0.1Nhydrochloric acid as the blank.Calculate the quantity,in mg,of C17H19ClN2S·HCl in each mLof the Injection taken by the formula:
12.5C(A254-A277)U/V(A254-A277)S,
in which Cis the concentration,in µg per mL,of USP Chlorpromazine Hydrochloride RSin the Standard solution,Vis the volume,in mL,of Injection taken,and the parenthetic expressions are the differences in the absorbances of the two solutions at the wavelengths indicated by the subscripts,for the solution from the Injection (U)and the Standard solution (S),respectively.
Auxiliary Information— Staff Liaison:Ravi Ravichandran,Ph.D.,Senior Scientist
Expert Committee:(PA3)Pharmaceutical Analysis 3
USP28–NF23Page 455
Phone Number:1-301-816-8330