Ianni Federica, Aroni Kyriaki, Gili Alessio, Sardella Roccaldo, Bacci Mauro, Lancia Massimo, Natalini Benedetto, Gambelunghe Cristiana
Drug Chemistry and Technology Section, Department of Pharmaceutics, University of Perugia, Italy.
Forensic and Sports Medicine Section, Department of Surgery and Biomedical Science, University of Perugia, Italy.
Drug Test Anal. 2018 Jun;10(6):968-976. doi: 10.1002/dta.2347. Epub 2018 Jan 25.
Pregabalin, a GABA analogue, binds to the alpha 2 delta subunit of voltage-dependent calcium channels. It is recognised as efficacious in pathologies such as epilepsy, neuropathic pain, and anxiety disorders. Since pregabalin prescriptions have increased worldwide, reports of its abuse have been accumulating, mainly in patients with opioid abuse disorders. The present study investigated potential pregabalin abuse by means of hair analysis, a matrix that provides valuable retrospective information. Half of the pool of 280 susceptible patients had been occasional drug users and were being monitored for driving licence renewals. The other 140 patients had a history of opiate dependency and were monitored to assess compliance with methadone therapy. In view of determining pregabalin in hair samples, it was extracted in methanol, successfully derivatised to give the ethyl chloroformate derivative, and finally pregabalin was analysed by gas chromatography-tandem mass spectrometry. Selectivity, linearity, limit of detection, limit of quantification, recovery, intra- and inter-day precision, and accuracy of the quantification procedure were appraised. Pregabalin limits of detection and quantification were 30 pg/mg and 50 pg/mg, respectively. We found 10.7% of hair samples from methadone patients and 4.29% from occasional drug users were positive to pregabalin without medical prescription. The mean pregabalin concentration in hair was higher than in consumers with medical indications (1.45 ng/mg vs 0.74 ng/mg). These results suggest that pregabalin possesses a significant abuse potential particularly among individuals attending opiate dependence services and that pregabalin abuse is a serious emerging issue, which should be carefully monitored.
普瑞巴林是一种γ-氨基丁酸(GABA)类似物,可与电压依赖性钙通道的α2δ亚基结合。它在癫痫、神经性疼痛和焦虑症等病症中被认为是有效的。由于普瑞巴林在全球范围内的处方量增加,其滥用报告也在不断积累,主要集中在患有阿片类药物滥用障碍的患者中。本研究通过毛发分析调查了普瑞巴林的潜在滥用情况,毛发这种基质能提供有价值的回顾性信息。280名易感患者中有一半曾是偶尔吸毒者,正在接受驾驶执照更新监测。另外140名患者有阿片类药物依赖史,接受监测以评估美沙酮治疗的依从性。为了测定毛发样本中的普瑞巴林,将其在甲醇中萃取,成功衍生化得到氯甲酸乙酯衍生物,最后通过气相色谱-串联质谱法分析普瑞巴林。评估了定量程序的选择性、线性、检测限、定量限、回收率、日内和日间精密度以及准确性。普瑞巴林的检测限和定量限分别为30 pg/mg和50 pg/mg。我们发现,在美沙酮患者的毛发样本中,10.7%对普瑞巴林呈阳性反应,在偶尔吸毒者中这一比例为4.29%,且均无医疗处方。毛发中普瑞巴林的平均浓度高于有医疗指征的使用者(1.45 ng/mg对0.74 ng/mg)。这些结果表明,普瑞巴林具有显著的滥用潜力,尤其是在接受阿片类药物依赖治疗的个体中,且普瑞巴林滥用是一个严重的新出现问题,应予以密切监测。