Lorazepam Oral Concentrate

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 Oral Concentrate 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

Mobile phase: Acetonitrile, glacial acetic acid, and water (45:0.2:55)

System suitability solution: 0.1 mg/mL each of USP Lorazepam RS and USP Lorazepam Related Compound E RS in methanol

Standard solution: 0.05 mg/mL of USP Lorazepam RS in methanol

Sample solution: Nominally 0.05 mg/mL of lorazepam prepared as follows. Transfer a suitable volume of Oral Concentrate to a volumetric flask, and dilute with methanol to volume.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm. For Identi

cation B, use a diode-array detector in the range of 220–400 nm.

Column: 4-mm × 30-cm; packing L1

Flow rate: 2 mL/min

Injection volume: 20 μL

System suitability

Samples: System suitability solution and Standard solution

[Note—The relative retention times for lorazepam and lorazepam related compound E are 0.6 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 2.0 between lorazepam and lorazepam related compound E, 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 Oral Concentrate 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 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: Methanol and 0.05 M monobasic ammonium phosphate (64:36)

Diluent: Methanol and 0.05 M monobasic ammonium phosphate (50:50). Adjust with ammonium hydroxide to a pH of 6.5.

System suitability solution: 0.04 mg/mL of USP Lorazepam RS, and 0.032 mg/mL each of USP Lorazepam Related Compound C RS and USP

Lorazepam Related Compound D RS in Diluent

Standard stock solution: 1.0 mg/mL of USP Lorazepam RS in methanol

Standard solution 1: 0.16 μg/mL of lorazepam from the Standard stock solution in Diluent

Standard solution 2: 0.16 μg/mL of USP Lorazepam Related Compound B RS, and 3.2 μg/mL each of USP Lorazepam Related Compound C

RS and USP Lorazepam Related Compound D RS in Mobile phase

Sample solution: Nominally 0.16 mg/mL of lorazepam prepared as follows. Transfer a suitable volume of Oral Concentrate to a volumetric flask, and dilute with Mobile phase to volume.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 240 nm

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

Flow rate: 0.7 mL/min

Injection volume: 20 μL

System suitability

Samples: System suitability solution and Standard solution 1

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% for lorazepam, Standard solution 1

Analysis

Samples: Standard solution 2 and Sample solution

[Note—Disregard peaks eluting prior to lorazepam related compound D.]

Calculate the percentage of lorazepam related compound B, lorazepam related compound C, and lorazepam related compound D in the portion of Oral Concentrate taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of lorazepam related compound B, 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 (mg/mL)

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

Acceptance criteria: See Table 1.

Table 1

^a Includes the sum of lorazepam related compound C and lorazepam related compound D.

5 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed, light-resistant containers, and 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

USP Lorazepam Related Compound E RS

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

C₁₅H₁₀Cl₂N₂O 305.16