Quantification of a New Anti-Cancer Molecule MJC13 Using a Rapid, Sensitive, and Reliable Liquid Chromatography-Tandem Mass Spectrometry Method.

Abstract

MJC13 is a novel molecule that has potential use for the treatment of hormone refractory prostate cancer (HRPC). The purpose of this work was to develop a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for quantification of MJC13. Itraconazole was used as the internal standard (IS). Acetonitrile was used to extract MJC13 from rat plasma and urine samples. A LC system equipped with a Waters XTerra MS C₁₈ column (125Å, 3.5 µm, 4.6×150 mm) was used for chromatographic separation with acetonitrile-water as mobile phase. The API 3200 QTRAP triple quadrupole mass spectrometer was used for chromatographic analysis by multiple reaction monitoring (MRM) at positive mode with the transitions m/z 272→m/z 162 for MJC13, and m/z 705→m/z 392 for IS. The retention times for MJC13 and IS were 4.98 min and 4.42 min, respectively. The standard curves of MJC13 in solution, rat plasma, and rat urine were linear in the concentration range of 1 - 1000, 1 - 1000 and 1 - 200 ng/mL, respectively. The intra- and inter-day accuracy (relative error) ranged from 1.99 - 4.20% and 1.83 - 4.39%, respectively. The intra- and inter-day precision (coefficient of variation) ranged from 2.27 - 3.88% and 2.80 - 4.79%, respectively. The extraction recovery rates of rat plasma and urine samples were 95.3% and 96.2%, respectively. No measurable matrix effect interfered with MJC13 identification and quantification in rat plasma and urine. In summary, a rapid, specific, sensitive, and reproducible LC-MS/MS method was developed and validated to quantify MJC13 in solution, rat plasma, and rat urine.