Olanzapine and Fluoxetine Capsules
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).
IDENTIFICATION
• The retention times of the major peaks in the Sample solution correspond to those in the Standard solution, as obtained in the Assay.
ASSAY
• 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:
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
Chromatographic system
Mode:
LC
Detector:
UV 227 nm
Column:
4.6-mm × 7.5-cm; 3.5-µm packing L7
Column temperature:
40
Flow rate:
2 mL/min
Injection size:
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
Calculate the percentage of C17H18F3NO in the portion of Capsules taken:
Samples:
Standard solution and Sample solution
Calculate the percentage of C17H20N4S in the portion of Capsules taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response of olanzapine from the Sample solution |
| rS | = | = peak response of olanzapine from the Standard solution |
| CS | = | = concentration of USP Olanzapine RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of olanzapine in the Sample solution (mg/mL) |
Result = (rU/rS) × (CS/CU) × (Mr1/Mr2) × 100
| rU | = | = peak response of fluoxetine from the Sample solution |
| rS | = | = peak response of fluoxetine from the Standard solution |
| CS | = | = concentration of USP Fluoxetine Hydrochloride RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of fluoxetine in the Sample solution (mg/mL) |
| Mr1 | = | = molecular weight of fluoxetine, 309.33 |
| Mr2 | = | = molecular weight of fluoxetine hydrochloride, 345.79 |
Acceptance criteria:
90.0%–110.0%
PERFORMANCE TESTS
• Dissolution 
711
Calculate the percentage of fluoxetine dissolved:
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 final concentration of L/1000 mg/mL each, where L is the Capsule label claim, in mg
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 olanzapine dissolved:
Result = (rU/rS) × (CS/L) × V × 100
| rU | = | = peak response of olanzapine from the Sample solution |
| rS | = | = peak response of olanzapine from the Standard solution |
| CS | = | = concentration of USP Olanzapine RS in the Standard solution (mg/mL) |
| L | = | = label claim for olanzapine (mg/Capsule) |
| V | = | = volume of Medium, 900 mL |
Result = (rU/rS) × (CS/L) × Mr1/Mr2 × V × 100
| rU | = | = peak response of fluoxetine from the Sample solution |
| rS | = | = peak response of fluoxetine from the Standard solution |
| CS | = | = concentration of USP Fluoxetine Hydrochloride RS in the Standard solution (mg/mL) |
| L | = | = label claim for fluoxetine (mg/Capsule) |
| Mr1 | = | = molecular weight of fluoxetine, 309.33 |
| Mr2 | = | = molecular weight of fluoxetine hydrochloride, 345.79 |
| V | = | = volume of Medium, 900 mL |
Tolerances:
NLT 80% (Q) of the labeled amount of olanzapine (C17H20N4S) and fluoxetine (C17H18F3NO) are dissolved.
• Uniformity of Dosage Units 905:
Meet the requirements
905:
Meet the requirements
IMPURITIES
Organic Impurities
• Procedure
Buffer and Mobile phase:
Proceed as directed in the Assay.
Standard solution:
2 µg/mL of USP Olanzapine RS and 8 µg/mL of USP Fluoxetine Hydrochloride RS in Mobile phase
System suitability solution:
0.1 mg/mL of USP Olanzapine RS, 0.11 mg/mL of USP Fluoxetine Hydrochloride RS, 0.002 mg/mL each of 
[(2-methylamino)ethyl] benzyl alcohol, trifluoro-p-cresol, USP Fluoxetine Related Compound B RS, and USP Olanzapine Related Compound B RS in Mobile phase
[(2-methylamino)ethyl] benzyl alcohol, trifluoro-p-cresol, USP Fluoxetine Related Compound B RS, and USP Olanzapine Related Compound B RS in Mobile phase
Sample solution:
Transfer the sample to a suitable volumetric flask to obtain a concentration of 0.2 mg/mL of olanzapine and 0.27–1.7 mg/mL of fluoxetine in Mobile phase.
Chromatographic system
Mode:
LC
Detector:
UV 215 nm
Column:
4.6-mm × 25-cm; 5-µm packing L7
Temperature
Column:
35
Auto sampler:
5
Flow rate:
1.5 mL/min
Injection size:
50 µL
Run time:
1.5 times the retention time of fluoxetine
System suitability
Samples:
Standard solution and System suitability solution
Suitability requirements
[Note—Identify the peaks using Impurity Table 1. ]
Resolution:
NLT 1.9 between [(2-methylamino)ethyl] benzyl alcohol and olanzapine related compound B
[(2-methylamino)ethyl] benzyl alcohol and olanzapine related compound B
Tailing factor:
NMT 1.8 for olanzapine and fluoxetine
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 are related to olanzapine. ]
Calculate the percentage of each olanzapine related degradation product in the portion of Capsules taken:
Result = (rU/rS) × (CS/CU) × (1/F) × 100
| rU | = | = peak response of each individual impurity from the Sample solution |
| rS | = | = peak response of olanzapine from the Standard solution |
| CS | = | = concentration of USP Olanzapine RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of olanzapine in the Sample solution (mg/mL) |
| F | = | = relative response factor for olanzapine related compound B, 1.73; for all other olanzapine impurities, 1.0 |
[Note—Peaks eluting between a relative retention time of 0.63 and 1.0 are related to fluoxetine. ]
Calculate the percentage of each fluoxetine related degradation product in the portion of Capsules taken:
Result = (rU/rS) × (CS/CU) × (Mr1/Mr2) × 100
| rU | = | = peak response of each individual impurity from the Sample solution |
| rS | = | = peak response of fluoxetine from the Standard solution |
| CS | = | = concentration of USP Fluoxetine Hydrochloride RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of fluoxetine in the Sample solution (mg/mL) |
| Mr1 | = | = molecular weight of fluoxetine, 309.33 |
| Mr2 | = | = molecular weight of fluoxetine hydrochloride, 345.79 |
Acceptance criteria
Individual impurities
Fluoxetine related degradation product:
NMT 0.25%
Olanzapine related degradation product:
NMT 0.20%
Total impurities
Fluoxetine related degradation products:
NMT 0.40%
Olanzapine related degradation products:
NMT 0.8%
Impurity Table 1
| Name | Relative Retention Time |
|---|---|
| [(2-Methylamino)ethyl] benzyl alcohol |
0.22 |
| Olanzapine related compound Ba | 0.24 |
| Trifluoro-p-cresol | 0.30 |
| Fluoxetine related compound Bb | 0.31 |
| Olanzapine | 0.63 |
| Fluoxetine | 1.0 |
|
a
2-Methyl-10H-thieno-[2,3-b][1,5]benzodiazepin-4[5H]-one.
b
N-Methyl-3-phenylpropylamine.
[Note—Peak names provided for identification purposes only. ]
|
|
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in tight containers. Store at controlled room temperature.
• USP Reference Standards 11
11
USP Fluoxetine Hydrochloride RS 
Benzenepropanamine, N-methyl-gamma-[4-(trifluoromethyl)phenoxy]-, hydrochloride, ±.
C17H18F3NO·HCl 345.79
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Benzenepropanamine, N-methyl-gamma-[4-(trifluoromethyl)phenoxy]-, hydrochloride, ±.
C17H18F3NO·HCl 345.79
USP Fluoxetine Related Compound B RS
N-Methyl-3-phenylpropylamine.
C10H15N 149.23
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N-Methyl-3-phenylpropylamine.
C10H15N 149.23
USP Olanzapine RS
10H-Thieno[2,3-b][1,5]benzodiazepine, 2-methyl-4-(4-methyl-1-piperazinyl.
C17H20N4S 312.43
10H-Thieno[2,3-b][1,5]benzodiazepine, 2-methyl-4-(4-methyl-1-piperazinyl.
C17H20N4S 312.43
USP Olanzapine Related Compound B RS
2-Methyl-10H-thieno-[2,3-b][1,5]benzodiazepin-4[5H]-one.
C12H10N2OS 230.29
2-Methyl-10H-thieno-[2,3-b][1,5]benzodiazepin-4[5H]-one.
C12H10N2OS 230.29
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Hariram Ramanathan, M.S.
Associate Scientific Liaison 1-301-816-8313 |
(SM42010) Monographs - Small Molecules 4 |
| 711 |
Margareth R.C. Marques, Ph.D.
Senior Scientific Liaison 1-301-816-8106 |
(GCDF2010) General Chapters - Dosage Forms |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 4103
Pharmacopeial Forum: Volume No. 36(2) Page 423