A highly aqueous HPLC-PDA method for the assay of gabapentin and pregabalin: applications in pharmaceutical analysis, dissolution testing, and forensic screening.

INTRODUCTION

Gabapentinoids, particularly pregabalin (PGL) and gabapentin (GBP), are widely used for neurological and psychiatric conditions but are increasingly linked to misuse and forensic challenges. Their high polarity, zwitterionic nature, and lack of strong chromophores present significant analytical challenges, often requiring derivatisation or specialised chromatographic systems. This study aimed to develop and validate a green, derivatisation-free HPLC-PDA method for the simultaneous determination of PGL and GBP in pharmaceutical formulations and seized samples.

METHODS

Chromatographic separation was achieved on a Hypersil GOLD™ C18 column (150 × 3 mm, 3 µm). An isocratic, highly aqueous mobile phase of water:methanol (96:4, v/v) was used at a flow rate of 0.7 mL/min. Detection was performed at 205 nm. Method optimisation was supported by a 23 full factorial design. The method was validated in accordance with International Council for Harmonisation Q2(R2) guidelines, including linearity, accuracy, precision, specificity, robustness, and sensitivity.

RESULTS

The proposed method achieved effective separation without derivatisation, buffer systems, or specialised columns, while reducing organic solvent consumption compared to some reported methods. Calibration was linear over 5-60 μg/mL (r ≥ 0.9997). Accuracy ranged from 95%-103%. Intra- and inter-day precision (%RSD) values were below 5%. The limits of detection/quantification values were 0.31/1.03 μg/mL for PGL and 0.25/0.85 μg/mL for GBP. Dissolution studies confirmed rapid drug release meeting pharmacopoeial criteria. Application to seized samples revealed PGL content exceeding labelled values (106%-110%), while no peak corresponding to GBP was observed under the current HPLC-PDA conditions.

CONCLUSION

The proposed method provides a simple, reliable, and environmentally favourable analytical approach for the simultaneous determination of gabapentinoids without complex sample preparation. Its successful application to pharmaceutical analysis, dissolution testing, and forensic samples highlights its suitability for routine laboratory use and regulatory monitoring.