Abstract

Introduction: Orphenadrine citrate is chemically (±)-N, N-Dimethyl-2-[(o-methyl-a-phenyl benzyl) oxy] ethylamine citrate. It is used to treat painful muscle spasms (spasm of skeletal muscles), as well as the treatment of Parkinson’s disease. The salts of orphenadrine are available in two varieties, namely hydrochloride and citrate. The hydrochloride salt is used for the treatment of Parkinson’s disease while the citrates form as a skeletal muscle relaxant.

Method: In the present study, an isocratic reverse phase-HPLC method was developed and validated as per ICH guidelines. The chromatographic separation was achieved on Phenomenex^® Lux Cellulose 1 (250 mm x 4.6 mm i.d, 5 µm particle size) column using mobile phase system containing acetonitrile: 0.02M ammonium bicarbonate (75:25 v/v) at the flow rate of 1.0 mL/min, and UV detection was carried out at 241 nm. The described method was linear over the range of 2 – 10 µg/mL for (±) orphenadrine enantiomers with a correlation coefficient (r² = 0.999). The limits of detection and quantification were found to be 0.50 µg/mL and 2.00 µg/mL respectively, for 20µL injection volume. The recovery study of orphenadrine from tablet formulation was found to be 102.21%. Orphenadrine standard solution and mobile phase were found to be stable for at least 48h. The orphenadrine enantiomers were well resolved with mean retention times of about 4.78 min and 6.00 min respectively.

Conclusion: The developed method was extensively validated and proved to be robust, accurate, precise and suitable for analysis of orphenadrine enantiomers in tablet dosage form and stability studies of orphenadrine.

Keywords: Chirality, ICH, orphenadrine citrate, RP-HPLC, validation.

Graphical Abstract