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• W1995772783 abstract "A robust and sensitive method using liquid chromatography–tandem mass spectrometry was developed and validated for the simultaneous determination of a novel topoisomerase 1 inhibitor CH0793076 (3076), the prodrug CH4556300 (TP300), and the active metabolite CH0793011 (3011) in human plasma. All plasma analyzed with this method was acidified with 1 M HCl and 46% citric acid solution in a ratio of 100:10:1 (v:v:v) to avoid the pH-based degradation of TP300 and to shift the equilibria of 3076 and 3011 between the lactone and carboxylate forms towards the lactone forms. After the plasma proteins were precipitated with methanol:acetonitrile:HCl 1 M (50:50:1, v:v:v) containing stable isotopic internal standards, the analytes were trapped on an Xterra MS C18 column (10 × 2.1 mm i.d., 5 μm) and separated on a Gemini C18 column (50 × 2.0 mm i.d., 5 μm) using column-switching liquid chromatography. Electrospray ionization in the positive-ion mode and multiple reaction monitoring were used to quantify the analytes with transitions m/z 587.2 > 441.2 for TP300, 459.1 > 415.2 for 3076, and 475.1 > 361.1 for 3011. The inter- and intra-day precisions were below 12%, and the accuracy was between −16% and 16% at the lower limit of quantitation (LLOQ) and between −11% and 14% at the other quality controls. The LLOQs of TP300, 3076, and 3011 were 0.8, 0.04, and 0.04 ng/mL, respectively. The validated method was successfully applied to clinical sample analysis and incurred sample reanalysis was also conducted." @default.
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• W1995772783 date "2011-11-01" @default.
• W1995772783 modified "2023-09-27" @default.
• W1995772783 title "Method development and validation of the simultaneous determination of a novel topoisomerase 1 inhibitor, the prodrug, and the active metabolite in human plasma using column-switching LC–MS/MS, and its application in a clinical trial" @default.
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• W1995772783 doi "https://doi.org/10.1016/j.jchromb.2011.09.015" @default.
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