A: Dissolve about 25mg of USP Droperidol RSin 10mLof water containing 0.3mLof 50%acetic acid in a separator to obtain a solution containing about 2.5mg per mL.Transfer a volume of Injection,equivalent to about 25mg of droperidol,to a second separator.Separately add 2mLof ammonia TSto each separator,and mix.Extract each solution with two 10-mLportions of chloroform,collecting the chloroform extracts from the solutions in separate 50-mLbeakers.Apply separately 20µLof the test solution and the Standard solution to a thin-layer chromatographic plate (see Chromatography á621ñ)coated with a 0.25-mm layer of chromatographic silica gel.Allow the spots to dry,and develop the chromatogram in a chamber with an unequilibrated solvent system consisting of a mixture of ethyl acetate,chloroform,methanol,and acetate buffer (0.2Msodium acetate adjusted with 50%acetic acid to a pHof 4.7)(54:23:18:5)until the solvent front has moved about three-fourths of the length of the plate.Remove the plate from the developing chamber,mark the solvent front,and allow the solvent to evaporate.Locate the spots on the plate by lightly spraying with dinitrophenylhydrazine TS,then examine under short-wavelength UVlight:the RFvalue of the principal spot obtained from the test solution corresponds to that obtained from the Standard solution.

B: The retention time of the major peak in the chromatogram of the Assay preparationcorresponds to that in the chromatogram of the Standard preparationas obtained in the Assay.

Mobile phase,System suitability preparation,Standard stock preparation,Standard preparation,andChromatographic system— Proceed as directed in the Assay.

Test preparation— Use the Assay preparation.

Procedure— Inject a volume (about 100µL)of the Test preparationinto the chromatograph,record the chromatogram of twice the retention time of droperidol,and measure the peak responses.Calculate the percentage of each impurity in the portion of Droperidol taken by the formula: in which riis the peak response for each impurity,and rsis the sum of the responses of all the peaks:the sum of all impurities is not more than 2.0%.

Borate buffer— Dissolve 31g of boric acid in about 800mLof water.Slowly add sodium hydroxide solution (1in 5)in small quantities until all of the boric acid is dissolved and the pHis constant at 7.0.Quantitatively transfer the solution to a glass-stoppered,1000-mLvolumetric flask,dilute with water to volume,and mix.

Mobile phase— Prepare a filtered and degassed mixture of methanol,water,and Borate buffer(700:280:20).Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).Standard stock preparation—Dissolve an accurately weighed quantity of USP Droperidol RSin methanol to obtain a solution having a known concentration of about 1mg per mL.

Standard preparation— Transfer 5.0mLof Standard stock preparationto a 100-mLvolumetric flask,dilute with Mobile phaseto volume,and mix.

System suitability preparation— Prepare a solution of 4¢-fluoroacetophenone in methanol containing about 1mg per mL.Transfer 5.0mLof this solution and 5.0mLof Standard stock preparationto a 100-mLvolumetric flask,dilute with Mobile phaseto volume,and mix.

Assay preparation— Transfer an accurately measured volume of Injection,equivalent to about 5mg of droperidol,to a 100-mLvolumetric flask,dilute with Mobile phaseto volume,and mix.

Chromatographic system (see Chromatography á621ñ)— The liquid chromatograph is equipped with a 280-nm detector and a 4.6-mm ×25-cm column that contains 10-µm packing L1.The flow rate is about 1.0mLper minute.Chromatograph the System suitability preparationand the Standard preparation,and record the peak responses as directed for Procedure:the resolution,R,between 4¢-fluoroacetophenone and droperidol is not less than 5.0;the tailing factor for the analyte peak is not more than 2.0;and the relative standard deviation for replicate injections of the Standard preparationis not more than 1.5%.

Procedure— Separately inject equal volumes (about 10µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the quantity,in mg,of droperidol (C22H22FN3O2)in each mLof the Injection taken by the formula: in which Cis the concentration,in mg per mL,of USP Droperidol 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.