Highly sensitive method for the determination of JI‐101, a multi‐kinase inhibitor in human plasma and urine by LC‐MS/MS‐ESI: method validation and application to a clinical pharmacokinetic study

Abstract

A highly sensitive, rapid assay method has been developed and validated for the estimation of JI-101 in human plasma and urine using LC-MS/MS-ESI in the positive-ion mode. The assay procedure involves extraction of JI-101 and alfuzosin (internal standard, IS) from human plasma/urine with a solid-phase extraction process. Chromatographic resolution was achieved on two Zorbax SB-C(18) columns connected in series with a PEEK coupler using an isocratic mobile phase comprising acetonitrile-0.1% formic acid in water (70:30, v/v). The total run time was 2.0 min. The MS/MS ion transitions monitored were 466.20 → 265.10 for JI-101 and 390.40 → 156.10 for IS. The method was subjected to rigorous validation procedures to cover the following: selectivity, sensitivity, matrix effect, recovery, precision, accuracy, stability and dilution effect. In both matrices the lower limit of quantitation was 10.0 ng/mL and the linearity range extended from ~10.0 to 1508 ng/mL in plasma or urine. The intra- and inter-day precisions were in the ranges 1.57-14.5 and 6.02-12.4% in plasma and 0.97-15.7 and 8.66-10.2% in urine. This method has been successfully applied for the characterization of JI-101 pharmacokinetics in cancer patients.

Quantitation of VEGFR2 (vascular endothelial growth factor receptor) inhibitors – review of assay methodologies and perspectives

“…The most abundant fragment ion was found at m / z 265, resulting from breakage of the amino ketone group. All publications have indicated same observations for the selection of ions for multiple reaction monitoring (Gurav et al ., , ; Sharma et al ., ).…”

“…() reported that, after acidification with 2% acetic acid, the samples were injected directly onto to the system; the recovery was found to be more than 70% compared with Sharma et al . (), where it was 50%.…”

“…Sharma et al . () reported a method for JI‐101 for the extraction of human plasma and urine using Oasis HLB cartridges followed by evaporation and finally reconstitution with mobile phase. In a modified SPE approach, Gurav et al .…”

“…A reliable assay for the quantification of JI‐101 was established using commercially available drugs, namely alfuzosin (Sharma et al ., ) and phenacetin (Gurav et al ., 2011, 2012).…”

“…Among all of the published methods (Gurav et al ., , ; Sharma et al ., ), octa‐decyl silane has been used as stationary phase. The mobile phase selected was a combination of acetonitrile and water with formic acid, which served as a pH modifier.…”