Quantification of pregabalin using hydrophilic interaction HPLC-high-resolution MS in postmortem human samples: eighteen case reports

Abstract

Pregabalin is a drug for treating epilepsy, anxiety disorders and neuropathic pain. Cases of poisoning are rare, though some have been fatal. Concentrations of pregabalin in postmortem human samples and its distribution have very rarely been documented. As the literature is so scarce, we propose to report the concentrations in autopsy samples of 18 people who had been taking Lyrica(®), including one case of a mixed overdose involving pregabalin. Analysis was carried out using an original Hydrophilic Interaction LIquid Chromatography (HILIC) technique coupled with a high-resolution mass spectrometer (m/z 160.1334 ± 5 ppm). The sensitivity of the technique enables a quick and simple treatment of the samples by protein precipitation. The method was validated in the whole blood with detection and quantification limits of 0.025 and 0.060 µg/mL, respectively. Pregabalin was a likely factor in the cause of death in 3 of the 18 cases. In the other individuals, the concentrations ranged from 0.4 to 17.0 in the peripheral blood, 1.5 to 11.1 in the central blood, 126.6 to 2004.6 in the urine and 10.5 to 58.3 µg/mL in the bile, with median values of 5.6, 4.6, 534.6 and 17.7, respectively.