Lamotrigine (LTZ) is a phenyltriazine derivative which belongs to anti-epileptic drugs (AEDs) class and prescribed as mono- or adjunctive-therapy in treatment of epilepsy. Therapeutic drug monitoring (TDM) of AEDs provides a valid clinical tool in optimization of overall therapy. However, TDM is challenging due to the high biological samples (plasma/blood) storage/shipment costs and the limited availability of laboratories providing TDM services. Sampling in the form of dry plasma spot (DPS) or dry blood spot (DBS) are suitable alternative to overcome these issues.

We developed and validated a new method for quantification of LTZ in human plasma and DPS. The extraction of LTZ from plasma and DPS was performed using liquid-liquid extraction with diethyl ether and an extraction solution composed of diethyl ether- methyl tert–butyl ether– acetone (50:30:20, v/v/v), respectively. Lamotrigine- 13C3, d3 was used as internal standard (ISTD) and the chromatographic separation was achieved on Hypurity Advance C18 column (150 × 4.6 mm, 5 μm). Quantitative estimation of LTZ and ISTD was performed on a liquid chromatography tandem mass spectrometer coupled with electrospray ionization interface operated under positive mode of ionization. Calibration curves were linear (r² > 0.99) over the concentration range of 10–3020 ng/mL for both plasma and DPS. Statistical analysis provides insignificant difference between LTZ concentration extracted from plasma and DPS samples. The method is found suitable for application in clinical study and in therapeutic monitoring of LTZ. To the best of our knowledge this is the first report which describing a validated stability indicating assay for quantification of LTZ in dry plasma spot.

拉莫三嗪（LTZ）是苯基三嗪衍生物，属于抗癫痫药（AED）类，被指定为治疗癫痫的单药或辅助疗法。AED的治疗药物监测（TDM）为优化整体治疗提供了有效的临床工具。但是，由于高生物样品（血浆/血液）的存储/运输成本以及提供TDM服务的实验室的可用性有限，TDM具有挑战性。干血浆斑点（DPS）或干血斑（DBS）形式的采样是克服这些问题的合适选择。

我们开发并验证了一种定量人体血浆和DPS中LTZ的新方法。从血浆和DPS中提取LTZ的方法是使用乙醚进行液-液萃取，以及分别由乙醚-甲基叔丁基醚-丙酮（50:30:20，v / v / v）组成的萃取溶液。将Lamotrigine-13C3，d3用作内标（ISTD），并在Hypurity Advance C18色谱柱（150×4.6 mm，5μm）上完成色谱分离。LTZ和ISTD的定量估计是在液相色谱串联质谱仪上进行的，该质谱仪与在正电离模式下运行的电喷雾电离接口耦合。校准曲线是线性的（r ² > 0.99），血浆和DPS的浓度范围均为10–3020 ng / mL。统计分析提供了从血浆和DPS样品中提取的LTZ浓度之间的微小差异。已发现该方法适用于LTZ的临床研究和治疗监测。据我们所知，这是第一份报告，它描述了一种经验证的稳定性指示剂，用于定量测定干血浆斑点中的LTZ。