Olanzapine and Fluoxetine Capsules

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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1 DEFINITION 

Olanzapine and Fluoxetine Capsules contain an amount of Olanzapine and Fluoxetine Hydrochloride equivalent to NLT 90.0% and NMT 110.0% each of the labeled amount of olanzapine (C₁₇H₂₀N₄S) and  fluoxetine (C₁₇H₁₈F₃NO). 

2 IDENTIFICATION 

A. The retention times of the major peaks of the Sample solution correspond to those of the Standard solution, as obtained in the Assay. Add the following: 

B. The UV spectra of the major peaks of the Sample solution correspond to those of the Standard solution, as obtained in the Assay. 

3 ASSAY 

Change to read: Procedure 

Buffer: 37 mg/L of disodium ethylenediaminetetraacetate in water. Add 3.3 mL of phosphoric acid, and adjust with 50% sodium hydroxide to a pH of 2.5. Dissolve 8.7 g of sodium dodecyl sulfate in the resulting solution. 

Mobile phase: Acetonitrile and Buffer (1:1) 

Standard solution: 0.12 mg/mL of USP Olanzapine RS and 0.45 mg/mL of USP Fluoxetine Hydrochloride RS in Mobile phase Sample solution: Nominally 0.06–0.18 mg/mL of olanzapine and 0.25–0.5 mg/mL of  fluoxetine in Mobile phase from a counted number of Capsules prepared as follows. Place the Capsules (including shells) into a suitable volumetric  flask and ll to about half volume with Mobile phase. Mix for NLT 30 min. If disintegration is incomplete, sonicate for NMT 5 min. Dilute with Mobile phase to volume, mix, and  filter or centrifuge. 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 227 nm. For Identification B, use a diode array detector in the range of 210–400 nm.  Column: 4.6-mm × 7.5-cm; 3.5-µm packing L7 

Column temperature: 40° 

Flow rate: 2 mL/min 

Injection volume: 10 µL 

Run time: 2.5 times the retention time of olanzapine 

System suitability 

Sample: Standard solution 

[Note—The relative retention times for olanzapine and  fluoxetine are 1.0 and 1.5, respectively.] 

Suitability requirements 

Resolution: NLT 2.0 between olanzapine and  fluoxetine 

Relative standard deviation: NMT 2.0% for the olanzapine and  fluoxetine peaks 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of the labeled amount of olanzapine (C₁₇H₂₀N₄S) in the portion of Capsules taken: 

Result = (r_U/r_S) × (C_S/C_U) × 100 

r_U = peak response of olanzapine  from the Sample solution 

r_S = peak response of olanzapine  from the Standard solution 

C_S = concentration of USP olanzapine  RS in the Standard solution (mg/mL) 

C_U = nominal concentration of olanzapine  in the Sample solution (mg/mL) 

Calculate the percentage of the labeled amount of  fluoxetine (C₁₇H₁₈F₃NO) in the portion of Capsules taken: 

Result = (r_U/r_S) × (C_S/C_U) × (M_r1/M_r2) × 100 

r_U = peak response of fluoxetine  from the Sample solution 

r_S = peak response of fluoxetine  from the Standard solution 

C_S = concentration of USP Fluoxetine Hydrochloride RS in the Standard solution (mg/mL) 

C_U = nominal concentration of  fluoxetine in the Sample solution (mg/mL) 

M_r1 = molecular weight of  fluoxetine, 309.33 

M_r2 = molecular weight of  fluoxetine hydrochloride, 345.79 

Acceptance criteria: 90.0%–110.0%each of olanzapine and  fluoxetine  

4 PERFORMANCE TESTS

Dissolution 〈711〉 

Medium: 0.1 N hydrochloric acid; 900 mL, deaerated. [Note—Helium sparging recommended.] 

Apparatus 2: 50 rpm, with 3-prong sinkers 

Time: 30 min for both olanzapine and  fluoxetine 

Standard solution: USP Olanzapine RS and USP Fluoxetine Hydrochloride RS in Medium to obtain a nal concentration of (L/1000) mg/mL each, where L is label claim, in mg/Capsule. 

Sample solution: Pass a portion of the solution through a suitable  filter of 0.45-µm pore size. 

Buffer, Mobile phase, Chromatographic system, System suitability, and Analysis: Proceed as directed in the Assay. Calculate the percentage of the labeled amount of olanzapine (C₁₇H₂₀N₄S) dissolved: 

Result = (r_U/r ) × (C/L) × V × 100 

r_U = peak response of olanzapine from the Sample solution 

r_S = peak response of olanzapine from the Standard solution 

C = concentration of USP Olanzapine RS in the Standard solution (mg/mL) 

L = label claim for olanzapine (mg/Capsule) 

V = volume of Medium, 900 mL 

Calculate the percentage of the labeled amount of  fluoxetine (C₁₇H₁₈F₃NO) dissolved: 

Result = (r_U/r_S) × (C_S/L) × (M_r1/M_r2) × V × 100 

r_U = peak response of  fluoxetine from the Sample solution 

r_S = peak response of  fluoxetine from the Standard solution 

C_S = concentration of USP Fluoxetine Hydrochloride RS in the Standard solution (mg/mL) 

L = label claim for  fluoxetine (mg/Capsule) 

M_r1 = molecular weight of  fluoxetine, 309.33 

M_r2 = molecular weight of  fluoxetine hydrochloride, 345.79 

V = volume of Medium, 900 mL 

Tolerances: NLT 80% (Q) of the labeled amounts of olanzapine (C₁₇H₂₀N₄S) and  fluoxetine (C₁₇H₁₈F₃NO) are dissolved. 

Uniformity of Dosage Units 〈905〉: Meet the requirements 

5 IMPURITIES 

Change to read: 

Organic Impurities 

Buffer and Mobile phase: Prepare as directed in the Assay. 

System suitability solution: 0.1 mg/mL of USP Olanzapine RS, 0.11 mg/mL of USP Fluoxetine Hydrochloride RS, and 0.002 mg/mL each of α[(2-methylamino)ethyl] benzyl alcohol, triuoro-p-cresol, USP Fluoxetine Related Compound B RS, and USP Olanzapine Related Compound B RS in Mobile phase 

Sensitivity solution: 3 µg/mL of USP Olanzapine RS, 3 µg/mL of USP Fluoxetine Hydrochloride RS, and 0.06 µg/mL each of α[(2- methylamino)ethyl] benzyl alcohol, triuoro-p-cresol, USP Fluoxetine Related Compound B RS, and USP Olanzapine Related Compound B RS in Mobile phase  

Standard solution: 2 µg/mL of USP Olanzapine RS and 8 µg/mL of USP Fluoxetine Hydrochloride RS in Mobile phase Sample solution: Empty the Capsules, and combine the contents in a suitable container. The contents of the Capsules may be powdered in a mortar, if necessary. Transfer an amount of the sample to a suitable volumetric  flask to obtain nominally 0.2 mg/mL of olanzapine and 0.27–1.7 mg/mL of  fluoxetine, and ll to about 70% volume with Mobile phase. Mix for about 5 min. Dilute with Mobile phase to volume, mix, and  filter or centrifuge. 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 215 nm 

Column: 4.6-mm × 25-cm; 5-µm packing L7 

Temperatures 

Autosampler: 5° 

Column: 35° 

Flow rate: 1.5 mL/min 

Injection volume: 50 µL 

Run time: 1.5 times the retention time of  fluoxetine 

System suitability 

Samples: System suitability solution, Sensitivity solution,  and Standard solution 

Suitability requirements 

[Note—Identify the peaks using Table 1.] 

Table 1 

_a Fluoxetine related degradation product.

_b Olanzapine related degradation product. 

^c Any other degradation product with a relative retention time <0.63 except  fluoxetine related degradation products, and any degradation product with a relative retention time >1.0. 

^d Sum of all specified  fluoxetine related degradation products and any other  fluoxetine related degradation product with relative retention times between  0.63 and 1.0. 

^e Sum of all specified olanzapine degradation products, any other degradation product with a relative retention time <0.63 except  fluoxetine related degradation products, and any degradation product with relative retention time >1.0. 

Resolution: NLT 1.9 between α[(2-methylamino)ethyl] benzyl alcohol and olanzapine related compound B, System suitability solution Tailing factor: NMT 1.8 for olanzapine and  fluoxetine, System suitability solution and Standard solution 

Relative standard deviation: NMT 2.0% for the olanzapine and  fluoxetine peaks, Standard solution 

Signal-to-noise ratio: NLT 3 for the α[(2-methylamino)ethyl] benzyl alcohol peak, Sensitivity solution  Analysis 

Samples: Standard solution and Sample solution 

[Note—Peaks eluting before a relative retention time of 0.63 and after a relative retention time of 1.0, excluding any peak with relative retention times of 0.22, 0.30, and 0.31, are olanzapine related degradation products.] 

Calculate the percentage of each olanzapine related degradation product in the portion of Capsules taken: 

Result = (r_U/r_S) × (C_S/C_U) × (1/F) × 100 

r_U = peak response of each individual impurity from the Sample solution 

r_S = peak response of olanzapine from the Standard solution 

C_S = concentration of USP Olanzapine RS in the Standard solution (mg/mL) 

C_U = nominal concentration of olanzapine in the Sample solution (mg/mL) 

F = relative response factor (see Table 1) 

[Note—Peaks eluting at relative retention times of 0.22, 0.30, and 0.31, and any peaks between a relative retention time of 0.63 and 1.0, are  fluoxetine related degradation products.] 

Calculate the percentage of each  fluoxetine related degradation product in the portion of Capsules taken: 

Result = (r_U/r_S) × (C_S/C_U) × (M_r1/M_r2) × 100 

r_U = peak response of each individual impurity from the Sample solution 

r_S = peak response of  fluoxetine from the Standard solution 

C_S = concentration of USP Fluoxetine Hydrochloride RS in the Standard solution (mg/mL) 

C_U = nominal concentration of  fluoxetine in the Sample solution (mg/mL) 

M_r1 = molecular weight of  fluoxetine, 309.33 

M_r2 = molecular weight of  fluoxetine hydrochloride, 345.79 

Acceptance criteria: See Table 1. 

6 ADDITIONAL REQUIREMENTS 

Packaging and Storage: Preserve in tight containers. Store at controlled room temperature. 

Change to read: 

USP Reference Standards 〈11〉 

USP Fluoxetine Hydrochloride RS  

USP Fluoxetine Related Compound B RS 

N-Methyl-3-phenylpropylamine. 

C₁₀H₁₅N 149.24  

USP Olanzapine RS  

USP Olanzapine Related Compound B RS 

2-Methyl-10H-thieno-[2,3-b][1,5]benzodiazepin-4[5H]-one. 

C₁₂H₁₀N₂OS 230.29