Orphenadrine Citrate 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

Orphenadrine Citrate Injection is a sterile solution of Orphenadrine Citrate in Water for Injection, prepared with the aid of Sodium Hydroxide. It contains NLT 93.0% and NMT 107.0% of the labeled amount of orphenadrine citrate (C₁₈H₂₃NO · C₆H₈O₇).

2 IDENTIFICATION

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

B. Identification Tests - General 〈191〉, Citrate: Meets the requirements

3 ASSAY

Procedure

Buffer: 5.8 g/L of monobasic ammonium phosphate in water. Adjust with ammonium hydroxide or phosphoric acid to a pH of 7.9 ± 0.05.

Mobile phase: Methanol, acetonitrile, and Buffer (45:15:40)

System suitability solution: 0.01 mg/mL each of USP Orphenadrine Related Compound B RS, USP Orphenadrine Related Compound C RS, USP Methylbenzhydrol RS, and 0.9 mg/mL of USP Orphenadrine Citrate RS in Mobile phase

Standard solution: 0.9 mg/mL of USP Orphenadrine Citrate RS in Mobile phase

Sample solution: Nominally 0.9 mg/mL of orphenadrine citrate from a known volume of the Injection containing NLT 90 mg of orphenadrine citrate in Mobile phase

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 220 nm

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

Column temperature: 40°

Flow rate: 1.5 mL/min

Injection volume: 20 μL

Run time: NLT 2.5 times the retention time of orphenadrine

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 3.0 between orphenadrine related compound B and orphenadrine related compound C; NLT 3.0 between orphenadrine related compound C and methylbenzhydrol

Tailing factor: NMT 2.0, 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 orphenadrine citrate (C₁₈H₂₃NO · C₆H₈O₇) in the portion of the Injection 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 Orphenadrine Citrate RS in the Standard solution (mg/mL)

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

Acceptance criteria: 93.0%–107.0%

4 IMPURITIES

Organic Impurities

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

Standard solution: 0.002 mg/mL of USP Orphenadrine Citrate RS in Mobile phase

Sensitivity solution: 0.001 mg/mL of USP Orphenadrine Citrate RS from the Standard solution in Mobile phase

System suitability

Samples: System suitability solution, Standard solution, and Sensitivity solution

Suitability requirements

Resolution: NLT 3.0 between orphenadrine related compound B and orphenadrine related compound C; NLT 3.0 between orphenadrine related compound C and methylbenzhydrol

Tailing factor: NMT 2, Standard solution

Relative standard deviation: NMT 5.0%, Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each degradation product in the portion of Injection 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 orphenadrine from the Standard solution

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

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

F = relative response factor (see Table 1)

Acceptance criteria: See Table 1.

Table 1

^a Counter ion peak; not to be reported; not to be included in total impurities.

^b 2-(Di-o-tolylmethoxy)-N,N-dimethylethan-1-amine.

5 SPECIFIC TESTS

pH 〈791〉: 5.0–6.0

Bacterial Endotoxins Test 〈85〉: NMT 5.8 USP Endotoxin Units/mg of orphenadrine citrate

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 at controlled room temperature.

Change to read:

USP Reference Standards 〈11〉

USP Methylbenzhydrol RS

2-Methylbenzhydrol;

Also known as phenyl(o-tolyl)methanol.

C₁₄H₁₄O 198.26

USP Orphenadrine Citrate RS

USP Orphenadrine Related Compound B RS

N-Ethyl-N,N-dimethyl [2-(2- (ERR 1-Feb-2022) methylbenzhydryloxy)ethyl]ammonium chloride; also known as N-Ethyl-N,N-dimethyl-2-[phenyl(2 (ERR 1-Feb-2022)-tolyl)methoxy]ethanaminium chloride.

C₂₀H₂₈ClNO 333.90

USP Orphenadrine Related Compound C RS

N-Methyl [2-(2-methylbenzhydryloxy)ethyl]amine hydrochloride; also known as N-methyl-2-[phenyl(o-tolyl)methoxy]ethanamine hydrochloride.

C₁₇H₂₁NO · HCl 291.82