Hamdan Imad I, Alsous Mervat, Masri Amira Taher
School of Pharmacy, The University of Jordan, Amman, Jordan.
Department of Clinical Pharmacy and Therapeutics, Faculty of Pharmacy, Applied Sciences Private University, Amman, Jordan.
J Anal Methods Chem. 2017;2017:7846742. doi: 10.1155/2017/7846742. Epub 2017 Aug 7.
Levetiracetam (LVT) is a widely used antiepileptic drug (AED). A less invasive sampling method for therapeutic drug monitoring (TDM) would be very useful particularly for children. Saliva has been shown as an adequate sample for TDM of some AEDs. Due to the high hydrophilicity of LVT its separation on common stationary phases is quite a challenge so that previous methods for determination of LVT in saliva employed either gradient high performance liquid chromatographic (HPLC) system or mass spectrometer as a detector. In this study the retention behavior of LVT on some common stationary phases was examined, with C8 being the most retentive. A simple isocratic HPLC method that is based on simple protein precipitation was developed and validated for the determination of LVT in saliva. The method was applied to a sample group of epileptic children for the purpose of assessing potential correlation with plasma LVT levels and to investigate patient's compliance. The results confirmed a reasonable correlation between plasma and salivary levels of LVT ( = 0.9) which supports the use of saliva for TDM of LVT. The study also revealed a significant percentage of epileptic patients having LVT levels below the estimated therapeutic range.
左乙拉西坦（LVT）是一种广泛使用的抗癫痫药物（AED）。一种侵入性较小的治疗药物监测（TDM）采样方法将非常有用，尤其是对儿童而言。唾液已被证明是某些AED进行TDM的合适样本。由于LVT具有高亲水性，在常见固定相上进行分离颇具挑战，因此以往唾液中LVT的测定方法要么采用梯度高效液相色谱（HPLC）系统，要么使用质谱仪作为检测器。在本研究中，考察了LVT在一些常见固定相上的保留行为，其中C8的保留能力最强。开发了一种基于简单蛋白质沉淀的简单等度HPLC方法，并对其进行验证以测定唾液中的LVT。该方法应用于一组癫痫儿童样本，以评估与血浆LVT水平的潜在相关性，并调查患者的依从性。结果证实血浆和唾液中LVT水平之间存在合理的相关性（= 0.9），这支持将唾液用于LVT的TDM。该研究还显示，有相当比例的癫痫患者LVT水平低于估计的治疗范围。
