Development and Validation of an LC–MS/MS Method for Quantifying Gabapentin in Plasma: Application to a Pharmacokinetic Study in Cats

Abstract

Gabapentin (GBP), a γ-aminobutyric acid analogue used for neuropathic pain and epilepsy, can reduce cat stress and improve veterinary exam compliance. A sensitive LC-MS/MS assay was established and rigorously validated for quantifying GBP in feline plasma. The method employed acetonitrile-mediated protein precipitation to efficiently extract GBP and its internal standard, pregabalin (PGB). Chromatographic separation was achieved within 7 min using a C18 column (2.1 × 50 mm, 1.7 μm) with a gradient mobile phase comprising 0.1% (<i>v</i>/<i>v</i>) formic acid in water and acetonitrile. The pharmacokinetics of 25  mg/kg GBP was studied by single-dose oral and intravenous administration. The results demonstrated that the method exhibited satisfactory precision, accuracy and linearity. The pharmacokinetic results showed that the T_max, C_max, T_1/2 and AUC_0–t of GBP in cats after oral administration of 25  mg/kg were (1.83 ± 0.75) h, (13.94 ± 3.75) μg/mL, (5.60 ± 1.79) h and (115.54 ± 27.56) (μg/mL) h, respectively. The results of the study indicated that after intravenous administration of 25 mg/kg GBP, the C₀, T_1/2 and AUC_0–t were (58.82 ± 15.34) μg/mL, (3.87 ± 0.64) h and (160.44 ± 32.65) (μg/mL) h, respectively. The oral bioavailability of GBP in cats was (78.71 ± 18.55)%. In this study, a selective and sensitive LC-MS/MS method for the quantification of GBP in cat plasma was developed and validated. This method was successfully employed to assess the pharmacokinetics following the oral and intravenous administration of GBP in cats.