Olanzapine
C17H20N4S 312.43
10H-Thieno[2,3-b][1,5]benzodiazepine, 2-methyl-4-(4-methyl-1-piperazinyl)-;
2-Methyl-4-(4-methyl-1-piperazinyl)-10H-thieno [2,3-b][1,5] benzodiazepine
[132539-06-1].
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C17H20N4S 312.43
10H-Thieno[2,3-b][1,5]benzodiazepine, 2-methyl-4-(4-methyl-1-piperazinyl)-;
2-Methyl-4-(4-methyl-1-piperazinyl)-10H-thieno [2,3-b][1,5] benzodiazepine
[132539-06-1].DEFINITION
Olanzapine contains NLT 98.0% and NMT 102.0% of C17H20N4S, calculated on the anhydrous, solvent-free basis.
IDENTIFICATION
• B.
The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
ASSAY
• Procedure
Buffer:
Dissolve 6.9 g of monobasic sodium phosphate in 1 L water. Adjust with phosphoric acid to a pH of 2.5, and then dissolve 12 g of sodium dodecyl sulfate in the resulting solution.
Mobile phase:
Acetonitrile and Buffer (47:53)
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:
0.1 mg/mL of Olanzapine in Mobile phase
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
Sample:
System suitability solution
Suitability requirements
Resolution:
NLT 2.0 between olanzapine related compound A and olanzapine
Tailing factor:
0.8–1.5 for the olanzapine peak
Relative standard deviation:
NMT 1.0% for the olanzapine peak
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of olanzapine (C17H20N4S) in the portion of Olanzapine 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:
98.0%–102.0% on the anhydrous, solvent-free basis
IMPURITIES
• Residue on Ignition 
281
:
NMT 0.1%
281:
NMT 0.1%
• Heavy Metals, Method II 231:
NMT 10 ppm
231:
NMT 10 ppm
• Organic Impurities
Buffer:
Dissolve 13 g of sodium dodecyl sulfate in 1500 mL of water. Add 5 mL of phosphoric acid, and then adjust with a sodium hydroxide solution to a pH of 2.5.
Solution A:
Acetonitrile and Buffer (48:52)
Solution B:
Acetonitrile and Buffer (70:30)
Mobile phase:
See Table 1.
Table 1
| Time (min) |
Solution A (%) |
Solution B (%) |
|---|---|---|
| 0 | 100 | 0 |
| 10 | 100 | 0 |
| 20 | 0 | 100 |
| 25 | 0 | 100 |
| 27 | 100 | 0 |
| 35 | 100 | 0 |
Edetate disodium solution:
37 mg/L of edetate disodium in Buffer
Diluent:
Acetonitrile and Edetate disodium solution (40:60)
System suitability solution:
20 µg/mL of USP Olanzapine RS and 2 µg/mL each of USP Olanzapine Related Compound A RS and USP Olanzapine Related Compound B RS in Diluent
Standard solution:
2 µg/mL of USP Olanzapine RS in Diluent
Sample solution:
0.4 mg/mL of Olanzapine in Diluent
Chromatographic system
Mode:
LC
Detector:
UV 220 nm
Column:
4.6-mm × 25-cm; 5-µm packing L7
Temperature
Column:
35
Sample:
5
Flow rate:
1.5 mL/min
Injection size:
20 µL
System suitability
Sample:
System suitability solution
[Note—Identify the peaks using the Relative Retention Time values given in Table 2. ]
Suitability requirements
Resolution:
NLT 3.0 between olanzapine related compound A and olanzapine
Tailing factor:
NMT 1.5 for the olanzapine peak
Relative standard deviation:
NMT 2.0% from 4 replicate injections for the olanzapine peak
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of each impurity in the portion of Olanzapine taken:
Result = (rU/rS) × (CS/CU) × (1/F) × 100
| rU | = | = peak response of each 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 | = | = concentration of olanzapine in the Sample solution (mg/mL) |
| F | = | = relative response factor for each impurity from Table 2 |
Acceptance criteria:
See Table 2.
Table 2
| Name | Relative Retention Time |
Relative Response Factor |
Acceptance Criteria, NMT (%) |
|
|---|---|---|---|---|
| Olanzapine related compound Ba | 0.3 | 2.3 | 0.10 | |
| Olanzapine related compound Ab | 0.8 | 1.0 | 0.10 | |
| Olanzapine | 1.0 | — | — | |
| Any individual, unspecified impurity |
— | — | 0.10 | |
| Total impurities | — | — | 0.4 | |
|
a
2-Methyl-10H-thieno-[2,3-b][1,5] benzodiazepin-4[5H]-one.
b
5-Methyl-2-((2-nitrophenyl)amino)-3-thiophenecarbonitrile.
|
||||
SPECIFIC TESTS
• Water Determination, Method I 921:
NMT 1.0%
921:
NMT 1.0%
[Note—A suitable solvent system for water determination in ketones and aldehydes (e.g., Hydranal composite 5K-working medium K or Aquastar composite 5K-solvent KC or equivalent) is recommended. ]
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in well-closed containers, and store at room temperature.
• USP Reference Standards 11
11
USP Olanzapine RS
USP Olanzapine Related Compound A RS
5-Methyl-2-((2-nitrophenyl)amino)-3-thiophenecarbonitrile.
C12H9N3O2S 259.28
5-Methyl-2-((2-nitrophenyl)amino)-3-thiophenecarbonitrile.
C12H9N3O2S 259.28
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 |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 4102
Pharmacopeial Forum: Volume No. 34(3) Page 641