Search

CAT ((+)-(13aS)-deoxytylophorinine) is a novel anticancer drug belonging to phenanthroindolizidine alkaloids. A sensitive and reliable liquid chromatography–tandem mass spectrometry (LC–MS/MS) method for simultaneous quantification of CAT and its pharmacologically active 3-O-desmethyl metabolite (S-4) was developed and validated in rat plasma using rotundine as the internal standard (IS). CAT, S-4 and IS were extracted by acetonitrile protein precipitation and separated on an Eclipse XDB-C18 column (1.8 μm, 4.6 mm × 50 mm) with acetonitrile–water (27:73, v/v) mobile phase containing 0.1% formic acid at a 0.4 mL/min flow rate. Positive ion electrospray ionization in multiple reaction monitoring mode was employed to measure CAT, S-4 and IS by monitoring the transitions m/z 364.2 → 70.1 for CAT, 350.1 → 70.1 for S-4 and 356.2 → 192.2 for IS. Good linear correlation ( r 2 > 0.991) was achieved for CAT and S-4 over the range of 0.214–128.16 and 0.044–11.00 ng/mL, respectively. The lower limit of quantification was 0.214 ng/mL for CAT and 0.044 ng/mL for S-4, using 50 μL rat plasma samples. The intra- and inter-day precisions were not exceed 15% and the accuracy ranged between 94.80% and 108.22%. The average extraction recoveries of both analytes were greater than 94.62%. The method was successfully applied to the pharmacokinetic study of CAT and S-4 in rats after oral administration. [ABSTRACT FROM AUTHOR]

Nigella glandulifera Freyn et Sit is a folk medicinal plant, whose seeds show significant anticancer activities attributed to triterpene saponins and volatile oil. In this study, an in vitro cytotoxicity assay demonstrated that Nigella A, the major component of triterpene saponins extracted from N. glandulifera , exhibited growth inhibition in the human lung carcinoma A-549 cell line. Due to this potential activity, a reliable liquid chromatography–tandem mass spectrometry (LC–MS/MS) method to quantify Nigella A in rat plasma for a pharmacokinetic study was developed. Nigella A and pravastatin, as internal standard (IS), were extracted from rat plasma using acetonitrile to precipitate protein. Separation was performed on an Agilent Zorbax SB-Aq (3.0 × 150 mm, 3.5 μm) column using a gradient elution method with acetonitrile–0.1% formic acid in water at a flow rate of 0.35 mL/min. Detection was performed using an electrospray ionization in a negative ion multiple reaction monitoring mode. The deprotonated precursor to product ion transitions monitored for Nigella A and IS was at m / z 1352.7→882.6 and m / z 423.1→321.0, respectively. The linear range was 0.240–120 μg/mL with a square regression coefficient ( r = 0.9996). The intra-day and inter-day precision was less than 6.93%. The simple extraction procedure provided recovery ranged from 92.32 to 95.44% for both analyte and IS. The method was proved to be reliable, precise, and accurate, and was successfully applied to a pharmacokinetic study of Nigella A in rats after i.v. administration via the tail vein at doses of 10, 20, and 30 mg/kg. [ABSTRACT FROM AUTHOR]

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]