Olanzapine

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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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 CAS RN®: 132539-06-1; UNII: N7U69T4SZR. 

1 DEFINITION 

Olanzapine contains NLT 98.0% and NMT 102.0% of olanzapine (C₁₇H₂₀N₄S), calculated on the anhydrous, solvent-free basis. 

2 IDENTIFICATION 

Change to read: 

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K (CN 1-May-2020)

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay. 

3 ASSAY 

Procedure 

Buffer: Dissolve 6.9 g of monobasic sodium phosphate in 1 L of water. Adjust with phosphoric acid to a pH of 2.5, and 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 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 260 nm 

Column: 4.6-mm × 15-cm; 5-µm packing L7 

Flow rate: 1.5 mL/min 

Injection volume: 20 µL 

System suitability 

Sample: System suitability solution 

[Note—The relative retention times for olanzapine related compound A and olanzapine are 0.8 and 1.0, respectively.] 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 Tablets taken: 

Result = (r_U/r_S) × (C_S/C_U) × 100 

r_U = peak response from the Sample solution 

r_S = peak response from the Standard solution 

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

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

Acceptance criteria: 98.0%–102.0% on the anhydrous, solvent-free basis 

4 IMPURITIES 

Residue on Ignition 〈281〉: NMT 0.1% 

Organic Impurities 

Buffer: Dissolve 13 g of sodium dodecyl sulfate in 1500 mL of water. Add 5 mL of phosphoric acid, and 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

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 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 220 nm 

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

Temperatures 

Column: 35° 

Sample: 5° 

Flow rate: 1.5 mL/min 

Injection volume: 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 four 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 = (r_U/r_S) × (C_S/C_U) × (1/F) × 100 

r_U = peak response of each 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 = concentration of olanzapine in the Sample solution (mg/mL) 

F = relative response factor for each impurity from (see Table 2) 

Acceptance criteria: See Table 2. 

Table 2 

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

^b  5-Methyl-2-((2-nitrophenyl)amino)-3-thiophenecarbonitrile. 

^c 1-Chloromethyl-1-methyl-4-(2-methyl-10H-benzo[b]thieno[2,3-e][1,4]diazepin-4-yl)piperazin-1-ium chloride. 

5 SPECIFIC TESTS 

Water Determination, Method I〈921〉 

[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.] 

Acceptance criteria: NMT 1.0% 

6 ADDITIONAL REQUIREMENTS 

Packaging and Storage: Preserve in well-closed containers, and store at room temperature. 

USP Reference Standards 〈11〉 

USP Olanzapine RS 

USP Olanzapine Related Compound A RS 

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