Developing an UPLC-MSMS Method to Quantify a Novel Anticancer Chalcone BOC26P for Its Pharmacokinetic Study In vivo

ABSTRACT

Objective BOC26P is a potent anticancer candidate which inhibits microtubule polymerization and shows strongcytotoxic activity against numerous cancer cell lines and drug resistant cell lines. To support the pharmacokineticstudy of BOC26P, a rapid, selective and reproducible UPLC-MS/MS method was developed.Method Dexamethasone sodium phosphate (DSP) was used as an internal standard (IS). Following proteinprecipitation by using methanol-acetonitrile solution (11, v/v) with an internal standard DSP, the processedsamples were chromatographed on an UPLC X Bridge 71 TM C8 column (4.6 mm × 100 mm, 3.5 μm) with a mobilephase that consisted of acetonitrile and 2mmol/L ammonium acetate aqueous solution (containing 0.25%ammonia) with a gradient elution pumped at a flow rate of 0.4 mL/min. Mass spectrometric detection wasperformed in the positive electrospray ionization mode by multiple reaction monitoring (m/z 428.84→198.92 and472.90→434.93 for BOC26P and DSP, respectively). The quantification of BOC26P in rat plasma was fully verified.Results The linearity was established in the range of 50 to 2000 ng/mL(r2≥0.99). The recovery of BOC26P fromspiked plasma were ranged from 96.7% to 110.5%. This method showed acceptable accuracy (3.7% to 6.3%) andprecision (1.5% to 3.1%) both of intra- and inter-day.Conclusion The developed method was successfully applied for three intravenous dose (2, 5, 12.5 mg/kg BOC26P)pharmacokinetics in male and female rats