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A highly selective and sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed for the quantification of scicinib, a novel thiosemicarbazone analogue and anticancer agent in rat plasma. Protein precipitation with saturated EDTA solution and methanol was selected for sample preparation, and brodimoprim was employed as the internal standard (IS). The analytes were separated on a Symmetry C18column (200 × 4.6 mm i.d., 5 µm) by isocratic elution with a mobile phase consisting of methanol and 0.2 mM EDTA (75:25, v/v) at a flow rate of 0.4 mL/min. After electrospray ionization, the analyte and IS were recorded under selected reaction monitoring (SRM) mode. The chosen transition wasm/z313.0 → 267.9 for scicinib andm/z339.0 → 280.9 for IS, respectively. The validated linearity range is 5–5000 ng/mL, with the lower limit of quantitation of 5 ng/mL. The developed method was successfully applied to a pharmacokinetic study of scicinib in rats after a single intravenous administration of 5 mg/kg. [ABSTRACT FROM AUTHOR]

A simple and rapid liquid chromatography-tandem mass spectrometry (LC–MS/MS) method has been developed and validated for the quantitation of indirubin-5-nitro-3′-monoxime (5-NIO) in rat plasma using 5-chloro-5′-chloro-indirubinoxime as the internal standard. The sample preparation involved protein precipitation using acetonitrile. Separation was achieved on an Xterra column C18 (2.1 mm × 50 mm, i.d. 5 µm) using a mixture of 0.1% formic acid-water/acetonitrile (18:82, v/v) as the mobile phase at a flow rate of 300 µL/min. Quantitation was performed on a triple quadrupole mass spectrometer employing electrospray ionization and multiple reaction monitoring (MRM) in negative ion mode. The total chromatographic run time was 2.5 min, and the calibration curves of 5-NIO were linear (correlation coefficient range: 0.9989–0.9999) over the concentration range of 0.2–2000 ng/mL in rat plasma. Also, the detection limit of the method was 0.05 ng/mL and it showed good accuracy and precision within the concentration range of 0.45–376 ng/mL. This validated method was successfully applied to estimating the pharmacokinetic parameters of 5-NIO following intravenous administration of 5-NIO to rats. [ABSTRACT FROM AUTHOR]

A simple and specific LC-MS/MS method for the determination of FK506 in blood was developed, validated, and successfully applied in pharmacokinetic studies of the effect of silymarin on FK506 in rats. Blood samples were extracted by liquid-liguid extraction with methyl tert-butyl ether and separated on an Eclipse plus-C18 column (150 × 2.1 mm, 3.5 µm) with the mobile phase of acetonitrile-10 mM ammonium acetate buffer solution (80:20, v/v). FK506 was detected without interference in the multiple-reaction monitoring mode with positive electrospray ionization. Good linearity was achieved over a range of 2.0–200 ng mL−1. The intra- and inter-day precisions were less than 13.5 % for all concentrations of quality control samples. The recoveries of FK506 were 74.2–85.3 %. Although the mean Cmax and AUC0 − ∞ of FK506 were increased to some extent, there was no significant difference in the pharmacokinetic profile of FK506 after oral administration to rats in the presence and absence of silymarin (200 mg kg−1, 2 times/d for 14 d). [ABSTRACT FROM AUTHOR]