A:Infrared Absorption á197Fñ.

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

System suitability solution— Mix suitable quantities of butyric acid,valeric acid,and USP Valproic Acid Related Compound A RSin Valproic Acid to obtain a solution containing about 1.0µLper mL,1.0µLper mL,and 0.1µLper mL,respectively.

Test solution— Use Valproic Acid.

Chromatographic system (see Chromatography á621ñ)— The gas chromatograph is equipped with a flame-ionization detector and a 0.32-mm ×60-m column coated with a 0.3-µm film of phase G25.Helium is used as the carrier gas with a total flow rate of about 150mLper minute with a split flow ratio of 100:1.The injection port and detector temperatures are maintained at 240and 260,respectively.The chromatograph is programmed as follows.Initially the temperature of the column is equilibrated at 145for 48minutes,then the temperature is linearly increased at a rate of 5per minute to 190,and maintained at 190.Chromatograph the System suitability solution,and record the peak responses as directed for Procedure:the relative retention times are about 0.38for butyric acid,0.52for valeric acid,1.64for related compound A,and 1.0for valproic acid;the resolution,R,between butyric acid and valeric acid is not less than 23.0;the column efficiency determined from valeric acid is not less than 100,000theoretical plates;and the tailing factor for the valeric acid peak is not more than 1.5.The related compound Apeak must elute between 41and 50minutes and must have a peak area of not less than 0.01%relative to the valproic acid peak.

Procedure— Inject a volume (about 0.5µL)of the Test solutioninto the chromatograph,record the chromatogram,and measure the peak responses.Calculate the percentage of each impurity in the portion of Valproic Acid taken by the formula: in which riis the peak response for each impurity;and rsis the sum of the responses for all the peaks:not more than 0.1%of any individual impurity is found;and not more than 0.3%of total impurities is found.

Solvent— Use dimethyl sulfoxide.

Internal standard solution— Transfer about 1.2g of nonanoic acid to a 100-mLvolumetric flask,and dissolve in and dilute with heptane to volume.

Standard preparation— Dilute an accurately weighed quantity of USP Valproic Acid RSwith heptane to obtain a solution having a known concentration of about 10.0mg per mL.Transfer 5.0mLof this solution to a 50-mLvolumetric flask,add 5.0mLof Internal standard solution,dilute with heptane to volume,and mix.

Assay preparation— Transfer about 100mg of Valproic Acid,accurately weighed,to a 10-mLvolumetric flask,dilute with heptane to volume,and mix.Transfer 5.0mLof this solution to a 50-mLvolumetric flask,add 5.0mLof Internal standard solution,dilute with heptane to volume,and mix.

Chromatographic system(see Chromatography á621ñ)— The gas chromatograph is equipped with a flame-ionization detector and a 2.0-mm ×1.8-m column packed with 10%phase G34on 80-to 100-mesh support S1A.The carrier gas is helium.The flow rate is about 35mLper minute.The column,injection port,and detector temperatures are maintained at 175,275,and 300,respectively.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the relative retention times are about 1.0for valproic acid and 2.0for nonanoic acid;the resolution,R,between valproic acid and nonanoic acid is not less than 7.0;and the relative standard deviation for replicate injections is not more than 1.5%.

Procedure— Separately inject equal volumes (about 3µL)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 C8H16O2in the portion of Valproic Acid taken by the formula: in which Cis the concentration,in mg per mL,of USP Valproic Acid RSin the Standard preparation;and RUand RSare the peak response ratios of valproic acid to the internal standard obtained from the Assay preparationand the Standard preparation,respectively.