Fraser A D, MacNeil W, Isner A F, Camfield P R
Toxicology Laboratory, Victoria General Hospital, Halifax, Nova Scotia, Canada.
Ther Drug Monit. 1995 Apr;17(2):174-8. doi: 10.1097/00007691-199504000-00012.
Lamotrigine is an anticonvulsant drug soon to be introduced to the North American market. It is chemically unrelated to any currently available antiepileptic drug. The objective of this study was to develop a quantitative high-performance liquid chromatography assay for lamotrigine in serum. Lamotrigine was extracted from serum at alkaline pH into ethyl acetate after addition of the internal standard (BW725C78). After mixing, the organic layer was evaporated to dryness before dissolving the residue in methanol for isocratic separation on a RP-8 column (5 microns) with a mobile phase of water/0.5 M phosphate buffer at pH 6.5/acetonitrile (790/10/200) with eluant monitoring at 306 nm. Calibration was performed with five serum standards (2-32 microM and recovery averaged 88% at 25 microM. Between-run precision was 4.1 and 2.5% C.V. at 13.6 and 31.6 microM, respectively. At room temperature, lamotrigine was stable for a minimum of 7 days. Interference studies were performed on serum specimens containing commonly monitored drugs. The only potentially interfering drug was carbamazepine, which elutes 2.5 times longer than lamotrigine. We conclude that this is a reliable method for quantitation of lamotrigine in serum.
拉莫三嗪是一种即将投放北美市场的抗惊厥药物。其化学结构与目前任何一种抗癫痫药物均无关联。本研究的目的是建立一种定量测定血清中拉莫三嗪的高效液相色谱法。在加入内标物（BW725C78）后，将血清在碱性pH条件下用乙酸乙酯萃取拉莫三嗪。混合后，将有机层蒸发至干，然后将残渣溶于甲醇中，在RP - 8柱（5微米）上进行等度分离，流动相为水/0.5M pH 6.5的磷酸盐缓冲液/乙腈（790/10/200），在306nm处监测洗脱液。用五种血清标准品（2 - 32微摩尔）进行校准，在25微摩尔时回收率平均为88%。批间精密度在13.6和31.6微摩尔时分别为4.1%和2.5%（变异系数）。在室温下，拉莫三嗪至少稳定7天。对含有常用监测药物的血清标本进行了干扰研究。唯一可能产生干扰的药物是卡马西平，其洗脱时间比拉莫三嗪长2.5倍。我们得出结论，这是一种可靠的定量血清中拉莫三嗪的方法。
