A Simple Dried Blood Spot Assay for Therapeutic Drug Monitoring of Lamotrigine Salah AbuRuz 1,2,& , Mutasim Al-Ghazawi 1 , Yousef Al-Hiari 3 1 Department of Clinical Pharmacy, Faculty of Pharmacy, The University of Jordan, Amman, Jordan; E-Mail: aburuz@ju.edu.jo 2 Department of Pharmaceutical Care, University of Jordan Hospital, Amman, Jordan 3 Department of Pharmaceutical Sciences, Faculty of Pharmacy, The University of Jordan, Amman, Jordan Received: 6 October 2009 / Revised: 14 March 2010 / Accepted: 15 March 2010 Online publication: 11 April 2010 Abstract Blood spot collection cards can be easily used to obtain specimens for analysis of drugs for the purpose of therapeutic drug monitoring. In this work, the development and validation of a simple technique for the determination of lamotrigine from dried blood spots is described. The method is based on liquid chromatography with ultraviolet detection. The intra- and inter-day precision (measured by CV%) was less than 11%. The accuracy (measured by relative error %) was less than 12%. The limits of detection and quantification were calculated to be 0.12 and 0.2 lg mL -1 respectively. The small volume of blood required (10 lL), the short analysis time (less than 4 min), combined with the simplicity of the analytical technique makes this a useful procedure for monitoring lamotrigine concentrations. Our preliminary experience with the developed method indicated that it can be implemented in routine clinical setting. Keywords Column liquid chromatography Therapeutic drug monitoring Blood spots Lamotrigine Introduction Lamotrigine shows broad-spectrum effi- cacy against partial seizures, primarily and secondarily generalized tonic–clonic seizures, absence seizures, and, possibly, other seizure types [1]. Its primary mechanism of action is blocking voltage- dependent sodium channels, leading to inhibition of excitatory neurotransmitter release and stabilization of neuronal membranes [2]. Lamotrigine is a lipophilic weak base, and is well absorbed after oral administration. A retrospective survey [3] found median lamotrigine plasma concentrations in responders to be 7.9 mg L -1 (range 2.1–15.4) compared to 16 mg L -1 (range 7.9–19.4) in patients reporting adverse effects. These investiga- tors have suggested that a therapeutic range of 3–14 mg L -1 may be the most appropriate. Interindividual variability in lamo- trigine disposition is prominent and amplified by the influence of age, preg- nancy, disease states, and co-medication [4–6]. This variability provides the strongest evidence to support lamotri- gine therapeutic drug monitoring. The most common and potentially life- threatening adverse effect of lamotrigine is rash, which is occurring more fre- quently in children and is greater when lamotrigine is used with valproate [7–9]. Total body clearance of lamotrigine is reduced significantly by valproic acid through inhibition of hepatic metabo- lism [7]. Plasma concentrations of lam- otrigine were reduced two to threefold during co-medication with oral contra- ceptives [10]. Therefore, it has been suggested that lamotrigine concentra- tions should be monitored during con- comitant use with agents that are enzyme inhibitors or inducers, in order to mini- mize its adverse events [7, 10]. On the other hand, it is reasonable to characterize 2010, 71, 1093–1099 DOI: 10.1365/s10337-010-1569-y 0009-5893/10/06 Ó 2010 Vieweg+Teubner Verlag | Springer Fachmedien Wiesbaden GmbH Full Short Communication Chromatographia 2010, 71, June (No. 11/12) 1093