McLoughlin D A, Olah T V, Ellis J D, Gilbert J D, Halpin R A
Merck Research Laboratories, West Point, PA 19486, USA.
J Chromatogr A. 1996 Mar 1;726(1-2):115-24. doi: 10.1016/0021-9673(96)88660-2.
The 5HT1D agonist sumatriptan is efficacious in the treatment of migraines. MK-462 is a drug of the same class which is under development in our laboratories. Bioanalytical methods of high efficiency, specificity and sensitivity were required to support the preclinical and clinical programs. These assays were based on HPLC with tandem MS-MS detection. MK-462 and sumatriptan were extracted using an automated solid-phase extraction technique on a C2 Varian Bond-Elut cartridge. The n-diethyl analogues of MK-462 and sumatriptan were used as internal standards. The analytes were chromatographed using reversed-phase (nitrile) columns coupled via a heated nebulizer interface to an atmospheric pressure chemical ionization source. The chromatographic run times were less than 7 min. Both methods were precise, accurate and selective down to plasma concentrations of 0.5 ng/ml. The assay for MK-462 was adapted to separately monitor the unlabeled and 14C-labeled species of the drug following intravenous administration of radiolabeled material to man.
5-羟色胺1D受体激动剂舒马曲坦在偏头痛治疗中疗效显著。MK-462是我们实验室正在研发的同类药物。需要高效、特异且灵敏的生物分析方法来支持临床前和临床研究项目。这些分析方法基于配有串联质谱检测的高效液相色谱法。MK-462和舒马曲坦采用自动固相萃取技术，在C2瓦里安Bond-Elut柱上进行萃取。MK-462和舒马曲坦的N-二乙基类似物用作内标。分析物通过反相（腈基）柱进行色谱分离，该柱通过加热雾化器接口与大气压化学电离源相连。色谱运行时间不到7分钟。两种方法在血浆浓度低至0.5 ng/ml时都具有精密度、准确性和选择性。MK-462的分析方法经过调整，以便在向人体静脉注射放射性标记物质后，分别监测该药物的未标记和14C标记形式。
