Lorazepam

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

Lorazepam contains NLT 98.0% and NMT 102.0% of lorazepam, calculated on the dried basis.

2 IDENTIFICATION

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197A or 197K

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

Change to read:

Procedure

Mobile phase: Acetonitrile, glacial acetic acid, and water (50: 1.2: 50)

Diluent: Methanol and water (75:25)

Standard solution: 0.1 mg/mL of USP Lorazepam RS in Diluent

Sample solution: 0.1 mg/mL of Lorazepam in Diluent

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 230 nm

Column: 4.6-mm × 25-cm; 5-μm packing L1

Temperatures

Autosampler: (USP 1-Dec-2021) 4°

Column: 5°

Flow rate: 1 mL/min

Injection volume: 5 μL

Run time: NLT 8 times the retention time of lorazepam (USP 1-Dec-2021)

System suitability

Sample: Standard solution

(USP 1-Dec-2021)

Suitability requirements

Tailing factor: NMT 1.5 (USP 1-Dec-2021)

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of lorazepam (C₁₅H₁₀Cl₂N₂O₂) in the portion of Lorazepam taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of lorazepam from the Sample solution

r_S= peak response of lorazepam from the Standard solution

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

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

Acceptance criteria: 98.0%–102.0% on the dried basis

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.3%

Change to read:

Organic Impurities

Mobile phase and Diluent: Prepare as directed in the Assay.

System suitability solution: 3.2 mg/mL of USP Lorazepam RS and 32 μg/mL each of USP Lorazepam Related Compound A RS, USP

Lorazepam Related Compound B RS, USP Lorazepam Related Compound C RS, USP Lorazepam Related Compound D RS, and USP

Lorazepam Related Compound E RS in Diluent

Sensitivity solution: 0.16 μg/mL of USP Lorazepam Related Compound B RS in Diluent (USP 1-Dec-2021)

Standard solution: 3.2 (USP 1-Dec-2021) μg/mL of USP Lorazepam RS in Diluent

Sample solution: 3.2 mg/mL of Lorazepam in Diluent

Chromatographic system: Proceed as directed in the Assay, except for Injection volume. (USP 1-Dec-2021)

Injection volume: 100 μL

System suitability

Samples: System suitability solution, Sensitivity solution, (USP 1-Dec-2021) and Standard solution

[Note—See Table 1 for the relative retention times.]

(USP 1-Dec-2021)

Suitability requirements

Resolution: NLT 1.2 between lorazepam related compound A and lorazepam related compound E, System suitability solution

(USP 1-Dec-2021)

Relative standard deviation: NMT 5% for lorazepam, Standard solution

Signal-to-noise ratio: NLT 10 for lorazepam related compound B, Sensitivity solution (USP 1-Dec-2021)

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Lorazepam 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 lorazepam from the Standard solution

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

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

F = relative response factor for any given impurity (see Table 1)

Acceptance criteria: See Table 1.

Table 1

5 SPECIFIC TESTS

Loss on Drying 〈731〉

Analysis: Dry under vacuum at 105° for 3 h.

Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight, light-resistant containers.

USP Reference Standards 〈11〉

USP Lorazepam RS

USP Lorazepam Related Compound A RS

7-Chloro-5-(o-chlorophenyl)-1,3-dihydro-3-acetoxy-2H-1,4-benzodiazepin-2-one.

C₁₇H₁₂Cl₂N₂O₃ 363.20

USP Lorazepam Related Compound B RS

2-Amino-2′,5-dichlorobenzophenone.

C₁₃H₉Cl₂NO 266.12

USP Lorazepam Related Compound C RS

6-Chloro-4-(o-chlorophenyl)-2-quinazolinecarboxaldehyde.

C₁₅H₈Cl₂N₂O 303.14

USP Lorazepam Related Compound D RS

6-Chloro-4-(o-chlorophenyl)-2-quinazolinecarboxylic acid.

C₁₅H₈Cl₂N₂O₂ 319.14

USP Lorazepam Related Compound E RS

6-Chloro-4-(o-chlorophenyl)-2-quinazoline methanol.

C₁₅H₁₀Cl₂N₂O 305.16