Abstract

STABILITY-INDICATING HPTLC METHOD DEVELOPMENT AND VALIDATION FOR SIMULTANEOUS ESTIMATION OF GABAPENTIN AND NORTRIPTYLINE IN BULK DRUG AND MARKETED FORMULATION

Deepanti Gajjar*, Kinjal Parmar, Prit K. Soni

Abstract

Gabapentin and nortriptyline are co-formulated (100 mg/10 mg and 200 mg/10 mg strengths) and used for the management of neuropathic pain, yet no stability-indicating high-performance thin-layer chromatographic (HPTLC) method for their simultaneous estimation has been reported to date. The present work describes the development and validation of a simple, rapid, precise and stability-indicating HPTLC method for the simultaneous determination of gabapentin and nortriptyline in bulk drug and in a marketed tablet formulation, in accordance with ICH Q1A(R2) and Q2(R1) guidelines. Chromatographic separation was achieved on pre-coated silica gel 60 F254 aluminium plates using methanol:acetonitrile:ethyl acetate:ammonia (5:3:3:0.1, v/v/v/v) as the mobile phase, with densitometric scanning at 236 nm for nortriptyline and, after post-chromatographic derivatization with 2% ninhydrin reagent, at 487 nm for gabapentin. The retention factor (Rf) values of nortriptyline and gabapentin in the mixture were 0.372 and 0.235, respectively. The method was linear over 200–450 ng/band (r² = 0.9956) for nortriptyline and 6000–8500 ng/band (r² = 0.991) for gabapentin. Mean recoveries ranged from 98.9–100.5%, and intraday/ inter-day precision (%RSD) was below 2% for both analytes. The limit of detection/limit of quantification were 176.89/536.05 ng/band for nortriptyline and 281.70/853.63 ng/band for Qgabapentin. The method was robust to small deliberate changes in mobile-phase composition and chamber saturation time, and was specific in the presence of degradation products generated under acid, base, oxidative, thermal and photolytic stress. Assay of the marketed formulation (Gabapin NT 300) gave 99.0% and 99.25% of the labelled claim for gabapentin and nortriptyline, respectively. The validated method is suitable for routine quality control and stability testing of gabapentin–nortriptyline combination products.

Keywords: Gabapentin; Nortriptyline; HPTLC; Stability-indicating method; Method validation; ICH Q2 (R1); Forced degradation.