Determination of mitomycin C in rat plasma by liquid chromatography-tandem mass spectrometry and its application for determining pharmacokinetics in rat

液相色谱-串联质谱法测定大鼠血浆中的丝裂霉素C及其在大鼠体内药代动力学研究中的应用

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作者:Kyung-Sun Moon, Jong-Min Song, JiMin Yi, Quynh Khoa Pham, Sung-Hoon Ahn

Abstract

To develop the liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for measuring mitomycin C in rat plasma, samples were processed using solid-phase extraction, with the internal standard being carbamazepine. A reversed phased C18 column was utilized for the LC-MS/MS study, and mobile phases consisting of 0.1 % formic acid in acetonitrile and water were injected into it at a rate of 0.3 mL/min. Multiple reaction monitoring in positive-ion mode with precursor-product ion pairs 335.3 → 242.3 (mitomycin C) and 237.1 → 194.1 (carbamazepine) was employed to quantify the compounds. The linear range in plasma was found to be 10-4000 ng/mL (r2 = 0.992). The inter-batch and intra-batch precision were <14.3 % (LLOQ: 14.7 %) and 13.4 % (LLOQ: 16.1 %), respectively. The recovery and the matrix effect of mitomycin C in plasma were 113 % and 111 %, respectively. Mitomycin C was stable under the conditions of this assay method. In the end, this approach proved effective in a pharmacokinetic investigation with the intravenous and oral administration of mitomycin C to rats.

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