A: Infrared Absorption á197Kñ—Obtain the test specimen as follows.Transfer a quantity of Capsule contents,equivalent to about 10mg of fluoxetine,to a suitable container,dissolve in 10mLof methanol,and filter.Rinse the container and filter with 5mLof methanol,and evaporate with the aid of a current of air and mild heat to dryness.

Medium: water;900mL.

Apparatus 2: 50rpm.

Time: 30minutes.

Diethylamine phosphate suspension— Transfer 250mLof acetonitrile to a suitable container,add 1.0mLof diethylamine,mix,and adjust with phosphoric acid to a pHof 3.5.[NOTE—Diethylamine phosphate will precipitate;therefore,keep well-mixed.]

Mobile phase— Prepare a filtered and degassed mixture of water,acetonitrile,and diethylamine (600:400:4),and adjust with phosphoric acid to a pHof 3.5.Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).

Standard solution— Prepare a solution of USP Fluoxetine Hydrochloride RShaving a concentration similar to that of the Test solution,and filter.Transfer 5.0mLof this solution to a suitable container,add 2.0mLof Diethylamine phosphate suspension,and mix.

Test solution— Filter 20mLof the solution under test.Transfer 5.0mLof this solution to a suitable container,add 2.0mLof Diethylamine phosphate suspension,and mix.

Chromatographic system (see Chromatography á621ñ)— The liquid chromatograph is equipped with a 226-nm detector and a 4.6-mm ×15-cm column that contains packing L10.The flow rate is about 2.0mLper minute.Chromatograph the Standard solution,and record the peak responses as directed for Procedure:the relative standard deviation for replicate injections is not more than 2.0%.

Procedure— Separately inject equal volumes (about 50µL)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 fluoxetine (C17H18F3NO)dissolved by the formula: in which 309.33and 345.79are the molecular weights of fluoxetine and fluoxetine hydrochloride,respectively;Cis the concentration,in µg per mL,of USP Fluoxetine Hydrochloride RSin the Standard solution;and rUand rSare the peak responses obtained from the Test solutionand the Standard solution,respectively.

Tolerances— Not less than 80%(Q)of the labeled amount of C17H18F3NOis dissolved in 30minutes.

Triethylamine buffer— Proceed as directed in the Assayunder Fluoxetine Hydrochloride.

Mobile phase— Prepare a filtered and degassed mixture of Triethylamine bufferand acetonitrile (65:35).Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).

System suitability solution— Dissolve an accurately weighed quantity of USP Fluoxetine Hydrochloride RSin Mobile phase,and dilute quantitatively,and stepwise if necessary,with Mobile phaseto obtain a solution having a known concentration of about 0.01mg per mL.

Test solution— Remove,as completely as possible,the contents of not fewer than 20Capsules,and mix.Transfer an accurately weighed portion of the combined contents,equivalent to about 20mg of fluoxetine,to a 10-mLvolumetric flask,dissolve in and dilute with Mobile phaseto volume,and mix.

Chromatographic system(see Chromatography á621ñ)— The liquid chromatograph is equipped with a 215-nm detector and a 4.6-mm ×25-cm column that contains 5-µm packing L10.The flow rate is about 1mLper minute.Chromatograph the System suitability solutionfor at least 22minutes,and record the peak responses as directed for Procedure:the column efficiency is not less than 1100theoretical plates,and the relative standard deviation for replicate injections is not more than 2.0%.

Procedure— Inject a volume (about 10µL)of the Test solutioninto the chromatograph,record the chromatograms,and measure the peak responses.Calculate the percentage of each impurity in the portion of Capsules taken by the formula: in which riis the peak response for each impurity;and rsis the sum of the responses of all of the peaks:not more than 0.25%of any individual impurity is found,and not more than 0.40%of total impurities is found.

Triethylamine buffer,Mobile phase,Standard preparation,and Chromatographic system— Proceed as directed in the Assayunder Fluoxetine Hydrochloride.

Assay preparation— Remove,as completely as possible,the contents of not fewer than 20Capsules,and mix.Transfer an accurately weighed portion of the powder,equivalent to about 10mg of fluoxetine,to a 100-mLvolumetric flask,dissolve in and dilute with Mobile phaseto volume,mix,and filter.

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 C17H18F3NOin the portion of Capsules taken by the formula: in which 309.33and 345.79are the molecular weights of fluoxetine and fluoxetine hydrochloride,respectively;Cis the concentration,in mg per mL,of USP Fluoxetine Hydrochloride RSin the Standard preparation;and rUand rSare the peak responses obtained from the Assay preparationand the Standard preparation,respectively.