Fluoxetine Hydrochloride
(floo ox' e teen hye'' droe klor' ide).
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345.79Benzenepropanamine, N-methyl-
-[4-(trifluoromethyl)phenoxy]-, hydrochloride, (±).
(±)-N-Methyl-3-phenyl-3-[(
,,-trifluoro-p-tolyl)oxy]propylamine, hydrochloride
[59333-67-4].» Fluoxetine Hydrochloride contains not less than 98.0 percent and not more than 102.0 percent of C17H18F3NO·HCl, calculated on the anhydrous basis.
Packaging and storage—
Preserve in tight containers.
USP Reference standards 
11
—
11—
USP Fluoxetine Hydrochloride RS 
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USP Fluoxetine Related Compound A RS
N-Methyl-3-phenyl-3-[(,,-(trifluoro-m-tolyl)oxy]propylamine hydrochloride.
C17H18F3NO·HCl 345.79
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N-Methyl-3-phenyl-3-[(
,,-(trifluoro-m-tolyl)oxy]propylamine hydrochloride.
C17H18F3NO·HCl 345.79
USP Fluoxetine Related Compound B RS
N-Methyl-3-phenylpropylamine.
C10H15N 149.24
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N-Methyl-3-phenylpropylamine.
C10H15N 149.24
Identification—
B:
A solution meets the requirements of the tests for Chloride 191.
191.
Water, Method I 921:
not more than 0.5%.
921:
not more than 0.5%.
Heavy metals, Method II 231:
0.003%.
231:
0.003%.
Related compounds—
Mobile phase—
Proceed as directed in the Assay.
Test solution 1—
Transfer about 56 mg of Fluoxetine Hydrochloride, accurately weighed, to a 10-mL volumetric flask, dissolve in and dilute with Mobile phase to volume, and mix.
Test solution 2—
Transfer 2 mL of Test solution 1, accurately measured, to a 10-mL volumetric flask, dilute with Mobile phase to volume, and mix.
System suitability solution—
Dissolve about 22 mg of USP Fluoxetine Hydrochloride RS in 10 mL of 1 N sulfuric acid, and heat to 85
for 3 hours. Cool, transfer 0.4 mL of this solution to a 25-mL volumetric flask, and add about 28 mg of USP Fluoxetine Hydrochloride RS, 1 mg of USP Fluoxetine Related Compound A RS, and 1 mg of USP Fluoxetine Related Compound B RS. Dilute with Mobile phase to volume, and mix.
for 3 hours. Cool, transfer 0.4 mL of this solution to a 25-mL volumetric flask, and add about 28 mg of USP Fluoxetine Hydrochloride RS, 1 mg of USP Fluoxetine Related Compound A RS, and 1 mg of USP Fluoxetine Related Compound B RS. 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 base-deactivated packing L7. The flow rate is about 1 mL per minute. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the relative retention times are about 0.24 for -[2-(methylamino)ethyl]benzenemethanol (if present), 0.27 for fluoxetine related compound B, 0.94 for fluoxetine related compound A, 1.0 for fluoxetine, and 2.17 for 4-trifluoromethylphenol; and the ratio of the height of the fluoxetine related compound A peak to the depth of the valley between the fluoxetine and fluoxetine related compound A peaks (measured from the fluoxetine related compound A peak height) is not more than 1.1.
621)—
The liquid chromatograph is equipped with a 215-nm detector and a 4.6-mm × 25-cm column that contains 5-µm base-deactivated packing L7. The flow rate is about 1 mL per minute. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the relative retention times are about 0.24 for -[2-(methylamino)ethyl]benzenemethanol (if present), 0.27 for fluoxetine related compound B, 0.94 for fluoxetine related compound A, 1.0 for fluoxetine, and 2.17 for 4-trifluoromethylphenol; and the ratio of the height of the fluoxetine related compound A peak to the depth of the valley between the fluoxetine and fluoxetine related compound A peaks (measured from the fluoxetine related compound A peak height) is not more than 1.1.
Procedure—
Separately inject equal volumes (about 10 µL) of Test solution 1 and Test solution 2 into the chromatograph, record the chromatograms for not less than twice the elution time for fluoxetine, and measure the peak responses. Calculate the percentage of fluoxetine related compound A in the portion of Fluoxetine Hydrochloride taken by the formula:
100rA / (rA + rU)
in which rA is the peak response of fluoxetine related compound A obtained from Test solution 2; and rU is the peak response of fluoxetine obtained from Test solution 2.
Calculate the percentage of each of the other impurities in the portion of Fluoxetine Hydrochloride taken by the formula:
100ri / (rs + 5rU)
in which ri is the peak response for each impurity obtained from Test solution 1; rs is the sum of the responses of all the peaks, excluding fluoxetine, obtained from Test solution 1; and rU is as defined above: not more than 0.15% of fluoxetine related compound A is found; not more than 0.25% of -[2-(methylamino)ethyl]benzenemethanol is found; not more than 0.25% of fluoxetine related compound B is found; and not more than 0.1% of any other individual impurity is found. The sum of all impurities found is not more than 0.5%.
-[2-(methylamino)ethyl]benzenemethanol is found; not more than 0.25% of fluoxetine related compound B is found; and not more than 0.1% of any other individual impurity is found. The sum of all impurities found is not more than 0.5%.
Assay—
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, stabilizer-free tetrahydrofuran, and methanol (6:3:1). Make adjustments if necessary (see System Suitability under Chromatography 621).
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 0.11 mg per mL.
Assay preparation—
Transfer about 11 mg of Fluoxetine Hydrochloride, accurately weighed, to a 100-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 227-nm detector and a 4.6-mm × 25-cm column that contains 5-µm base-deactivated packing L7. 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%.
621)—
The liquid chromatograph is equipped with a 227-nm detector and a 4.6-mm × 25-cm column that contains 5-µm base-deactivated packing L7. 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 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 C17H18 F3NO·HCl in the portion of Fluoxetine Hydrochloride taken by the formula:
100C(rU / rS)
in which 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.
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Ravi Ravichandran, Ph.D.
Principal Scientific Liaison 1-301-816-8330 |
(SM42010) Monographs - Small Molecules 4 |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 3241
Pharmacopeial Forum: Volume No. 30(3) Page 848