Takasugi N, Mafune E, Yokokawa S, Toriyama K, Tsuchiya K, Sugimoto T
J Chromatogr. 1985 Aug 9;342(2):349-58. doi: 10.1016/s0378-4347(00)84526-0.
A method for the determination of malotilate (I), the corresponding monocarboxylic acid (II) and its decarboxylated product (III) in plasma is described. Plasma was extracted with chloroform spiked with internal standard. The residue, dissolved in methanol, was chromatographed on a reversed-phase column with a mobile phase of 60% acetonitrile and 1% acetic acid in water. The sensitivity limit for I, II and III was 50, 25 and 100 ng/ml of plasma, respectively. Compound I in the same plasma extract was also analysed by gas chromatography--electron-impact mass spectrometry. The base peaks m/z 160 for I and m/z 162 for internal standard (IV) were monitored; the sensitivity limit for I was 2.5 ng/ml of plasma. The determination of the metabolites of I, II and its conjugate (V), and isopropyl-hydrogen malonate (VI) in urine by high-performance liquid chromatography is also described. The limit of quantification for VI was 2.0 micrograms/ml, and the overall coefficient of variation of VI was 4.7%. The limit of quantification for II in urine was 0.5 micrograms/ml and that for V was 1.0 micrograms/ml as total II (II + V). The overall precision of the method was satisfactory. The method was used to determine plasma and urine concentrations in four dogs orally dosed with 100, 200 or 400 mg of malotilate.
本文描述了一种测定血浆中马洛替酯（I）、相应的单羧酸（II）及其脱羧产物（III）的方法。血浆用加有内标的氯仿萃取。残留物溶于甲醇后，在反相柱上进行色谱分析，流动相为60%乙腈和1%乙酸的水溶液。I、II和III的检测限分别为血浆50、25和100 ng/ml。同一份血浆提取物中的化合物I也通过气相色谱 - 电子轰击质谱法进行分析。监测I的基峰m/z 160和内标（IV）的m/z 162；I的检测限为血浆2.5 ng/ml。本文还描述了通过高效液相色谱法测定尿液中I、II及其共轭物（V）和异丙基氢丙二酸酯（VI）的代谢物。VI的定量限为2.0微克/ml，VI的总变异系数为4.7%。尿液中II的定量限为0.5微克/ml，V作为总II（II + V）的定量限为1.0微克/ml。该方法的总体精密度令人满意。该方法用于测定四只口服100、200或400 mg马洛替酯的犬的血浆和尿液浓度。
