Lorazepam Injection

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 Injection is a sterile solution of Lorazepam in a suitable medium. It contains NLT 90.0% and NMT 110.0% of the labeled amount of lorazepam (C₁₅H₁₀Cl₂N₂O₂).

2 IDENTIFICATION

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

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

3 ASSAY

Procedure

Buffer: 0.05 M monobasic ammonium phosphate

Mobile phase: Methanol and Buffer (50:50). Adjust with ammonium hydroxide to a pH of 6.5.

System suitability solution: 0.04 mg/mL of lorazepam and 32 μg/mL each of USP Lorazepam Related Compound C RS and USP Lorazepam

Related Compound D RS in Mobile phase

Standard stock solution: 1 mg/mL of USP Lorazepam RS in methanol

Standard solution: 0.16 mg/mL of USP Lorazepam RS in Mobile phase from the Standard stock solution

Sample solution: Nominally 0.16 mg/mL of lorazepam from Injection, diluted with Mobile phase

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 240 nm. For Identification B, use a diode array detector in the range of 210–400 nm.

Column: 4.6-mm × 10 to 15-cm; 5-μm packing L1

Flow rate: 2 mL/min

Injection volume: 20 μL

Run time: NLT 3 times the retention time of lorazepam

System suitability

Samples: System suitability solution and Standard solution

[Note—The relative retention times for lorazepam related compound D, lorazepam, and lorazepam related compound C are 0.7, 1.0, and 2.7, respectively.]

Suitability requirements

Resolution: NLT 1.2 between lorazepam related compound D and lorazepam; NLT 1.2 between lorazepam and lorazepam related

compound C, System suitability solution

Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of lorazepam (C₁₅H₁₀Cl₂N₂O₂) in the portion of Injection 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 = nominal concentration of lorazepam in the Sample solution (mg/mL)

Acceptance criteria: 90.0%–110.0%

4 IMPURITIES

Organic Impurities

Mobile phase, System suitability solution, Sample solution, and Chromatographic system: Proceed as directed in the Assay.

Standard solution 1: Prepare as directed for the Standard solution in the Assay.

Standard solution 2: 3.2 μg/mL each of USP Lorazepam Related Compound C RS and USP Lorazepam Related Compound D RS in Mobile phase

System suitability

Samples: System suitability solution and Standard solution 1

[Note—The relative retention times for lorazepam related compound D, lorazepam, and lorazepam related compound C are 0.7, 1.0, and 2.7, respectively.]

Suitability requirements

Resolution: NLT 1.2 between lorazepam related compound D and lorazepam; NLT 1.2 between lorazepam and lorazepam related compound C, System suitability solution

Relative standard deviation: NMT 2.0%, Standard solution 1

Analysis

Samples: Sample solution and Standard solution 2. Do not include as an impurity any peak from the Sample solution that has a retention

time shorter than that of the lorazepam related compound D peak from Standard solution 2.

Calculate the percentage of lorazepam related compound C and lorazepam related compound D in the portion of Injection taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of lorazepam related compound C or lorazepam related compound D from the Sample solution

r_S = peak response of the corresponding related compound from Standard solution 2

C_S = concentration of the corresponding related compound in Standard solution 2 (μg/mL)

C_U = nominal concentration of lorazepam in the Sample solution (μg/mL)

Calculate the percentage of any other impurity in the portion of Injection taken:

Result = (r_U/r_T) × 100

r_U = peak response of the individual impurity from the Sample solution

r_T = peak response of lorazepam from the Sample solution

Acceptance criteria: NMT 4.0% of all impurities

Limit of Lorazepam Related Compound B

Buffer: 0.05 M monobasic ammonium phosphate. Adjust with ammonium hydroxide to a pH of 6.5.

Mobile phase: Methanol and Buffer (55:45)

Diluent: Methanol and Buffer (50:50)

Standard solution: 0.16 μg/mL of USP Lorazepam Related Compound B RS in Diluent. Sonicate to dissolve if necessary.

Sample solution: Nominally 0.16 mg/mL of lorazepam from Injection, diluted with Diluent. Sonicate to dissolve if necessary.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 240 nm

Column: 4.6-mm × 10-cm; 5-μm packing L1

Flow rate: 2 mL/min

Injection volume: 50 μL

Run time: 1.5 times the retention time of lorazepam related compound B

System suitability

Sample: Standard solution

Suitability requirements

Relative standard deviation: NMT 5.0%

Signal-to-noise ratio: NLT 10

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of lorazepam related compound B in the portion of Injection taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of lorazepam related compound B from the Sample solution

r_S = peak response of lorazepam related compound B from the Standard solution

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

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

Acceptance criteria: NMT 0.1%

5 SPECIFIC TESTS

Bacterial Endotoxins Test 〈85〉: Contains NMT 102

USP Endotoxin Units/mg of lorazepam

Other Requirements: It meets the requirements in Injections and Implanted Drug Products 〈1〉.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in single-dose or multiple-dose containers, preferably of Type I glass, protected from light. Store in a refrigerator.

USP Reference Standards 〈11〉

USP Lorazepam RS

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