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

## TL;DR

A new LC-MS/MS method was developed to measure gabapentin in cat plasma, enabling a pharmacokinetic study to understand how the drug behaves in cats after oral and intravenous administration.

## Contribution

The study introduces a validated high-throughput LC-MS/MS method for quantifying gabapentin in feline plasma, with application to pharmacokinetic analysis.

## Key findings

- The developed LC-MS/MS method showed satisfactory precision, accuracy, and linearity for gabapentin quantification in cat plasma.
- Oral administration of 25 mg/kg gabapentin in cats resulted in a Tmax of 1.83 h, Cmax of 13.94 μg/mL, and oral bioavailability of 78.71%.
- Intravenous administration of 25 mg/kg gabapentin showed a C0 of 58.82 μg/mL and AUC0–t of 160.44 (μg/mL) h.

## Abstract

Gabapentin is an analogue of the neurotransmitter γ-aminobutyric acid, which is commonly used to treat neuropathic pain and epilepsy. However, studies have shown that early use of gabapentin can significantly reduce cats’ stress and increase their compliance with veterinary examinations. There is currently little research on the pharmacokinetics of gabapentin tablets for oral administration in cats. Consequently, monitoring gabapentin plasma levels provides critical insights into therapeutic adherence and facilitates early identification of toxicity thresholds. In this study, a novel LC-MS/MS assay was established and comprehensively validated to achieve high-throughput quantification of gabapentin in feline plasma resolution within 7 min. Additionally, this study provides further clinical evaluation for the management of sedation and anti-stress in cats.

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% (v/v) 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 Tmax, Cmax, T1/2 and AUC0–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, T1/2 and AUC0–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.