Olanzapine Tablets

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 Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of olanzapine (C₁₇H₂₀N₄S). 

2 IDENTIFICATION 

Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K 

Standard: Dissolve 10 mg of USP Olanzapine RS in 10 mL of chloroform. Evaporate to dryness on a water bath maintained at 55°. Use about 2 mg of the residue to prepare a potassium bromide pellet. 

Sample: Crush NLT 5 Tablets, and transfer the powder equivalent to 30 mg of olanzapine to a suitable container. Add 30 mL of chloroform, and sonicate for 15 min to dissolve. Pass through a suitable filter, and evaporate the filtrate to dryness on a water bath maintained at 55°. Use about 2 mg of the residue to prepare a potassium bromide pellet. 

Acceptance criteria: Meet the requirements 

3 ASSAY 

Procedure 

[Note—A few drops of acetonitrile, not to exceed 5% of the nal volume, may be added to the Standard solution and Sample solution before nal dilution to reduce foaming.] 

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 (NLT 5), 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 

(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 

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

Acceptance criteria: 90.0%–110.0% 

4 PERFORMANCE TESTS 

Dissolution 〈711〉 

Test 1 

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: (L/1000) mg/mL of USP Olanzapine RS in Medium, where L is the label claim in mg/Tablet. 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 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 260 nm 

Column: 4.6-mm × 15-cm; 5-µm packing L10 

Flow rate: 1.5 mL/min 

Injection volume: 50 µL 

System suitability 

Sample: Standard solution 

Suitability requirements 

Relative standard deviation: NMT 2.0% 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of the labeled amount of olanzapine (C₁₇H₂₀N₄S) dissolved: 

Result = (r_U/r_S) × C_S × (V/L) × 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) 

V = volume of Medium, 900 mL 

L = label claim (mg/Tablet) 

Tolerances: NLT 80% (Q) of the labeled amount of olanzapine (C₁₇H₂₀N₄S) is dissolved. 

Test 2: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2. 

Medium: 0.1 N hydrochloric acid; 900 mL 

Apparatus 2: 50 rpm 

Time: 20 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. Pass through a suitable filter of 0.45-µm pore size. 

Standard stock solution: 0.28 mg/mL of USP Olanzapine RS prepared as follows. Transfer a suitable amount of USP Olanzapine RS to a suitable volumetric flask. Add about 8% of the nal flask volume of acetonitrile. Sonicate to dissolve the Reference Standard. Dilute with Medium to volume. 

Standard solution: (L/900) mg/mL of USP Olanzapine RS in Medium from Standard stock solution, where L is the label claim in mg/Tablet. 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 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 260 nm 

Column: 4.6-mm × 15-cm; 5-µm packing L11 

Column temperature: 40° 

Flow rate: 1.5 mL/min 

Injection volume: 50 µL 

System suitability 

Sample: Standard solution 

Suitability requirements 

Relative standard deviation: NMT 2.0% 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of the labeled amount of olanzapine (C₁₇H₂₀N₄S) dissolved: 

Result = (r_U/r_S) × C_S × (V/L) × 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) 

V = volume of Medium, 900 mL 

L = label claim (mg/Tablet) 

Tolerances: NLT 80% (Q) of the labeled amount of olanzapine (C₁₇H₂₀N₄S) is dissolved. 

Uniformity of Dosage Units 〈905〉: Meet the requirements 

5 IMPURITIES 

Change to read: 

Organic Impurities 

[Note—A few drops of acetonitrile, not to exceed 5% of the nal volume, may be added to the Standard solution and Sample solution before nal dilution to reduce foaming.] 

Buffer 1: 3.3 mL/L of phosphoric acid. Adjust with 50% sodium hydroxide 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: 0.002 mg/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: Nominally 0.375–0.500 mg/mL of olanzapine from a suitable number of Tablets prepared as follows. Transfer a known quantity of Tablets to a suitable volumetric flask, and dilute with Diluent to volume. 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 Table 1. 

Table 1 

6 Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 220 nm 

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

Column temperature: 35° 

Flow rate: 1.5 mL/min 

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

r_U = peak response of each degradation product 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 2) 

Acceptance criteria: See Table 2. 

^a(Z)-3-(Hydroxymethylene)-4-(4-methylpiperazin-1-yl)-1,3-dihydro-2H-benzo[b][1,4]diazepine-2-thione.

^b(Z)-4-(4-Methylpiperazin-1-yl)-3-(2-oxopropylidene)-1H-benzo[b][1,4]diazepin-2(3H)-one. 

^c(Z)-1-{4-(4-Methylpiperazin-1-yl)-2-thioxo-1H-benzo[b][1,4]diazepin-3(2H)-ylidene}propan-2-one. 

^d(Z)-(4-(4-Methylpiperazin-1-yl)-2-thioxo-1,2-dihydro-3H-benzo[b][1,4]diazepin-3-ylidene)methyl acetate. 

7 ADDITIONAL REQUIREMENTS 

Packaging and Storage: Preserve in tight, light-resistant containers, and store at controlled room temperature. 

Labeling: When more than one Dissolution test is given, the labeling states the Dissolution test used only if Test 1 is not used. 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 

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