Olanzapine Tablets
DEFINITION
Olanzapine Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of olanzapine (C17H20N4S).
IDENTIFICATION
• Infrared Absorption 
197S
197S
Standard solution:
1 mg/mL of USP Olanzapine RS in chloroform
Sample solution:
Dissolve a quantity of powdered Tablets, equivalent to 30 mg of olanzapine, in 30 mL of chloroform, and filter. Evaporate completely to dryness with the aid of a current of air. Redissolve the residue in 1 mL of chloroform.
ASSAY
• Procedure
Buffer 1:
6.9 g/L of monobasic sodium phosphate. Adjust with phosphoric acid to a pH of 2.5.
Buffer 2:
12 g/L of sodium dodecyl sulfate in Buffer 1
Mobile phase:
Acetonitrile and Buffer 2 (1:1)
System suitability solution:
0.1 mg/mL of USP Olanzapine RS and 0.01 mg/mL of USP Olanzapine Related Compound A RS in Mobile phase
Standard solution:
0.1 mg/mL of USP Olanzapine RS in Mobile phase
Sample solution:
Transfer a known quantity of Tablets, equivalent to NLT 25 mg of olanzapine, to a suitable volumetric flask. Dilute with Mobile phase to volume, mix, and sonicate for 10 min. Centrifuge a portion of this solution, and dilute the clear supernatant with Mobile phase to obtain a solution containing about 0.1 mg/mL of olanzapine. [Note—Agitation of the flask may be necessary before sonication to prevent Tablets from adhering to the flask, making disintegration and dissolution difficult. ]
Chromatographic system
Mode:
LC
Detector:
UV 260 nm
Column:
4.6-mm × 15-cm; 5-µm packing L7
Flow rate:
1.5 mL/min
Injection size:
20 µL
System suitability
Samples:
System suitability solution and Standard solution
[Note—The relative retention times for olanzapine related compound A and olanzapine are 0.89 and 1.0, respectively. ]
Suitability requirements
Resolution:
NLT 2.0 between olanzapine and olanzapine related compound A, System suitability solution
Tailing factor:
NMT 1.8, Standard solution
Relative standard deviation:
NMT 2.0%, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of C17H20N4S in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of USP Olanzapine RS in the Standard solution (mg/mL) |
| CU | = | = concentration of olanzapine in the Sample solution (mg/mL) |
Acceptance criteria:
90.0%–110.0%
PERFORMANCE TESTS
• Dissolution 711
711
Medium:
0.1 N hydrochloric acid; 900 mL
Apparatus 2:
50 rpm
Time:
30 min
Mobile phase:
10 g/L of ammonium acetate in a mixture of methanol and water (2:3). Adjust with hydrochloric acid to a pH of 4.0.
Standard solution:
An amount, in mg, corresponding to the Tablet label claim, of USP Olanzapine RS in 1000 mL of Medium. Transfer 5.0 mL of this solution to a tube, and add 2.0 mL of Mobile phase.
Sample solution:
Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size. Transfer 5.0 mL of the filtrate to a tube, and add 2.0 mL of Mobile phase.
Chromatographic system
Mode:
LC
Detector:
UV 260 nm
Column:
4.6 mm × 15 cm; 5-µm packing L10
Flow rate:
1.5 mL/min
Injection size:
50 µL
System suitability
Sample:
Standard solution
Suitability requirements
Relative standard deviation:
NMT 2.0%
Analysis
Calculate the percentage of olanzapine dissolved:
Result = (rU/rS) × (CS × V/L) × 100
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of USP Olanzapine RS in the Standard solution (mg/mL) |
| V | = | = volume of Medium, 900 mL |
| L | = | = label claim (mg/Tablet) |
Tolerances:
NLT 80% (Q) of the labeled amount of olanzapine is dissolved.
• Uniformity of Dosage Units 905:
Meet the requirements
905:
Meet the requirements
IMPURITIES
Organic Impurities
• Procedure
Buffer 1:
3.3 mL/L of phosphoric acid. Adjust with 50% NaOH to a pH of 2.5.
Buffer 2:
8.7 g/L of sodium dodecyl sulfate in Buffer 1
Buffer 3:
18.6 mg/L of edetate disodium (EDTA) in Buffer 2
Solution A:
Acetonitrile and Buffer 2 (12:13)
Solution B:
Acetonitrile and Buffer 2 (7:3)
Diluent:
Acetonitrile and Buffer 3 (2:3)
System suitability solution:
20 µg/mL of USP Olanzapine RS, and 2 µg/mL each of USP Olanzapine Related Compound B RS and USP Olanzapine Related Compound C RS in Diluent
Standard solution:
2 µg/mL of USP Olanzapine RS in Diluent
Sensitivity solution:
0.4 µg/mL of USP Olanzapine RS in Diluent, from the Standard solution
Sample solution:
Transfer a known quantity of Tablets to a suitable volumetric flask, and dilute with Diluent to volume to obtain a solution containing either 375 or 500 µg/mL of olanzapine (based on the label claim). Centrifuge a portion of this solution, and use the supernatant. [Note—Immediate agitation of the flask may be necessary to prevent Tablets from adhering to the flask, making dissolution and disintegration difficult. [Caution—Do not sonicate.
] The Sample solution is stable for 12 h at room temperature and 48 h if refrigerated. ]
Mobile phase:
See the gradient table below.
| Time (min) |
Solution A (%) |
Solution B (%) |
|---|---|---|
| 0 | 100 | 0 |
| 10 | 100 | 0 |
| 20 | 0 | 100 |
| 25 | 0 | 100 |
| 27 | 100 | 0 |
| 35 | 100 | 0 |
Chromatographic system
Mode:
LC
Detector:
UV 220 nm
Column:
4.6-mm × 25-cm; 5-µm packing L7
Temperature:
35
Flow rate:
1.5 mL/min
Injection size:
20 µL
System suitability
Samples:
System suitability solution, Standard solution, and Sensitivity solution
Suitability requirements
Resolution:
NLT 3.0 between olanzapine and olanzapine related compound C, System suitability solution
Tailing factor:
NMT 1.5 for the olanzapine peak, System suitability solution
Relative standard deviation:
NMT 2.0%, Standard solution
Signal-to-noise ratio:
NLT 10, Sensitivity solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of each impurity in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × (1/F) × 100
| rU | = | = peak response of each impurity from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of USP Olanzapine RS in the Standard solution (µg/mL) |
| CU | = | = concentration of olanzapine in the Sample solution (µg/mL) |
| F | = | = relative response factor for each impurity listed in Impurity Table 1 |
Acceptance criteria
Individual impurities:
See Impurity Table 1.
Total impurities:
NMT 1.5%
Impurity Table 1
| Name | Relative Retention Time |
Relative Response Factor |
Acceptance Criteria, NMT (%) |
|---|---|---|---|
| Olanzapine lactama | 0.26 | 1.0 | 0.50 |
| Olanzapine related compound Bb | 0.30 | 2.3 | 0.20 |
| Olanzapine thiolactamc | 0.34 | 1.0 | 0.50 |
| Olanzapine related compound Cd | 0.83 | 1.0 | 0.50 |
| Olanzapine | 1.0 | — | — |
| Any individual unspecified impurity | — | 1.0 | 0.20 |
|
a
(Z)-4-(4-Methylpiperazin-1-yl)-3-(2-oxopropylidene)-1H-benzo[b][1,4]diazepin-2(3H)-one.
b
2-Methyl-10H-thieno-[2,3-b][1,5] benzodiazepin-4[5H]-one.
c
(Z)-1-{4-(4-Methylpiperazin-1-yl)-2-thioxo-1H-benzo[b][1,4]diazepin-3(2H)-ylidene}propan-2-one.
d
2-Methyl-4-(4-methylpiperazin-1-yl)-10H-benzo[b]thieno[2,3-e][1,4]diazepine 4'-N-oxide.
|
|||
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in tight, light resistant containers, and store at controlled room temperature.
• USP Reference Standards 11
11
USP Olanzapine RS
USP Olanzapine Related Compound A RS
5-Methyl-2-((2-nitrophenyl)amino)-3-thiophenecarbonitrile.
5-Methyl-2-((2-nitrophenyl)amino)-3-thiophenecarbonitrile.
USP Olanzapine Related Compound B RS
2-Methyl-10H-thieno-[2,3-b][1,5]benzodiazepin-4[5H]-one.
2-Methyl-10H-thieno-[2,3-b][1,5]benzodiazepin-4[5H]-one.
USP Olanzapine Related Compound C RS
(2-Methyl-4-(4-methylpiperazin-1-yl)-10H-benzo[b]thieno[2,3-e][1,4]diazepine 4¢-N-oxide).
C17H20N4OS 328.43
(2-Methyl-4-(4-methylpiperazin-1-yl)-10H-benzo[b]thieno[2,3-e][1,4]diazepine 4¢-N-oxide).
C17H20N4OS 328.43
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 4105
Pharmacopeial Forum: Volume No. 35(2) Page 282