Fluoxetine Capsules
» Fluoxetine Capsules contain an amount of Fluoxetine Hydrochloride equivalent to not less than 90.0 percent and not more than 110.0 percent of the labeled amount of fluoxetine (C17H18F3NO).
Packaging and storage— Preserve in tight, light-resistant containers.
USP Reference standards 11
USP Fluoxetine Hydrochloride RS Click to View Structure
Identification—
A: Infrared Absorption 197K
Test specimen— Transfer a quantity of Capsule contents, equivalent to about 10 mg of fluoxetine, to a suitable container, dissolve in 10 mL of methanol, and filter. Rinse the container and filter with 5 mL of methanol, and evaporate with the aid of a current of air and mild heat to dryness.
Dissolution 711
Medium: water; 900 mL.
Apparatus 2: 50 rpm.
Time: 30 minutes.
Determine the amount of C17H18F3NO dissolved by employing the following method.
Diethylamine phosphate suspension— Transfer 250 mL of acetonitrile to a suitable container, add 1.0 mL of diethylamine, mix, and adjust with phosphoric acid to a pH of 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 pH of 3.5. Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard solution— Prepare a solution of USP Fluoxetine Hydrochloride RS having a concentration similar to that of the Test solution, and filter. Transfer 5.0 mL of this solution to a suitable container, add 2.0 mL of Diethylamine phosphate suspension, and mix.
Test solution— Filter 20 mL of the solution under test. Transfer 5.0 mL of this solution to a suitable container, add 2.0 mL of Diethylamine phosphate suspension, and mix.
Chromatographic system (see Chromatography 621)— 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 2.0 mL per 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 50 µL) of the Standard solution and the Test solution into 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:
(309.33/345.79)900C(rU / rS)
in which 309.33 and 345.79 are the molecular weights of fluoxetine and fluoxetine hydrochloride, respectively; C is the concentration, in µg per mL, of USP Fluoxetine Hydrochloride RS in the Standard solution; and rU and rS are the peak responses obtained from the Test solution and the Standard solution, respectively.
Tolerances— Not less than 80% (Q) of the labeled amount of C17H18F3NO is dissolved in 30 minutes.
Uniformity of dosage units 905: meet the requirements.
Chromatographic purity—
Triethylamine buffer— Proceed as directed in the Assay under Fluoxetine Hydrochloride.
Mobile phase— Prepare a filtered and degassed mixture of Triethylamine buffer and acetonitrile (65:35). Make adjustments if necessary (see System Suitability under Chromatography 621).
System suitability solution— 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 0.01 mg per mL.
Test solution— Remove, as completely as possible, the contents of not fewer than 20 Capsules, and mix. Transfer an accurately weighed portion of the combined contents, equivalent to about 20 mg of fluoxetine, to a 10-mL volumetric flask, dissolve in and 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 5-µm packing L10. The flow rate is about 1 mL per minute. Chromatograph the System suitability solution for at least 22 minutes, and record the peak responses as directed for Procedure: the column efficiency is not less than 1100 theoretical plates; and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure— Inject a volume (about 10 µL) of the Test solution into 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:
100(ri / rs)
in which ri is the peak response for each impurity; and rs is the sum of the responses of all the peaks: not more than 0.25% of any individual impurity is found, and not more than 0.80% of total impurities is found.
Assay—
Triethylamine buffer, Mobile phase, Standard preparation, and Chromatographic system— Proceed as directed in the Assay under Fluoxetine Hydrochloride.
Assay preparation— Remove, as completely as possible, the contents of not fewer than 20 Capsules, and mix. Transfer an accurately weighed portion of the powder, equivalent to about 10 mg of fluoxetine, to a 100-mL volumetric flask, dissolve in and dilute with Mobile phase to volume, mix, and filter.
Procedure— Separately inject equal volumes (about 10 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of fluoxetine (C17H18F3NO) in the portion of Capsules taken by the formula:
(309.33 / 345.79)100C(rU / rS)
in which 309.33 and 345.79 are the molecular weights of fluoxetine and fluoxetine hydrochloride, respectively; C is the concentration, in mg 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.
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