Solution— Transfer a volume of Oral Solution, equivalent to about 20 mg of fluoxetine, to a separatory funnel, add 5.0 mL of water and 0.5 mL of 1 N sodium hydroxide, extract with 5 mL of chloroform, and discard the aqueous layer. Evaporate the remaining layer to dryness, and dissolve the residue in 0.4 mL of chloroform.

FOR ORAL SOLUTION PACKAGED IN SINGLE-UNIT CONTAINERS: meets the requirements.

FOR ORAL SOLUTION PACKAGED IN MULTIPLE-UNIT CONTAINERS: meets the requirements.

Ion-pair solution— Transfer about 4.3 g of sodium 1-octanesulfonate and 13.8 g of monobasic sodium phosphate to a suitable container, dissolve in 1 L of water, and adjust with phosphoric acid to a pH of 3.0.

Diluent— Prepare a mixture of Ion-pair solution, methanol, and acetonitrile (6:3:1).

Solution A— Prepare a filtered and degassed mixture of Ion-pair solution, methanol, and acetonitrile (53:26:21).

Solution B— Prepare a filtered and degassed mixture of Ion-pair solution, acetonitrile, and methanol (43:35:22).

Mobile phase— Use variable mixtures of Solution A and Solution B as directed for Chromatographic system. Make adjustments if necessary (see System Suitability under Chromatography 621).

System suitability solution— Dissolve a quantity of USP Fluoxetine Hydrochloride RS in 1 N sulfuric acid to obtain a solution having a known concentration of about 2.0 mg per mL, and heat at 85 for 1 hour. Transfer 1.0 mL of this solution to a 100-mL volumetric flask, add about 10 mg of USP Fluoxetine Hydrochloride RS, dissolve in and dilute with Diluent to volume, and mix.

Test solution— Transfer an accurately measured volume of Oral Solution, equivalent to about 19 mg of fluoxetine, to a 10-mL volumetric flask, dilute with Diluent to volume, and mix.

Diluted test solution— Transfer 1.0 mL of the Test solution to a 25-mL volumetric flask, dilute with Diluent to volume, and mix.

Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 215-nm detector and a 4.6-mm × 25-cm column that contains packing L1. The flow rate is about 1 mL per minute. The chromatograph is programmed as follows. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the retention time of any peak, except the peak for fluoxetine, is less than 13 minutes.

Procedure— Separately inject equal volumes (about 20 µL) of the Diluted test solution and the Test solution into the chromatograph, record the chromatograms, and measure all of the peak responses. Calculate the percentage of each impurity in the volume of Oral Solution taken by the formula: in which ri is the peak response for each impurity obtained from the Test solution; and rS is the peak response for fluoxetine obtained from the Diluted test solution: not more than 0.4% of any individual impurity is found; and not more than 0.8% of total impurities is found.

(Official January 1, 2007)

Triethylamine buffer— Transfer about 10 mL of triethylamine, accurately measured, to a suitable container, add about 980 mL of water, and adjust with phosphoric acid to a pH of 6.0.

Mobile phase— Prepare a filtered and degassed mixture of Triethylamine buffer and acetonitrile (1:1). Make adjustments if necessary (see System Suitability under Chromatography 621).

Standard preparation— Dissolve an accurately weighed quantity of USP Fluoxetine Hydrochloride RS in Mobile phase, and dilute quantitatively, and stepwise if necessary, with Mobile phase to obtain a solution having a known concentration of about 45 µg per mL.

Assay preparation— Transfer an accurately measured volume of Oral Solution, equivalent to about 4.0 mg of fluoxetine, to a 100-mL volumetric flask, dilute with Mobile phase to volume, and mix.

Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 215-nm detector and a 4.6-mm × 25-cm column that contains packing L10. The flow rate is about 1 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the tailing factor is not more than 2.0; and the relative standard deviation for replicate injections is not more than 2.0%.

Procedure— Separately inject equal volumes (about 20 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the fluoxetine peak. Calculate the quantity, in mg, of fluoxetine (C17H18F3NO) in the volume of Oral Solution taken by the formula: in which 309.33 and 345.79 are the molecular weights for fluoxetine and fluoxetine hydrochloride, respectively; C is the concentration, in µg per mL, of USP Fluoxetine Hydrochloride RS in the Standard preparation; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.