Determination of a Novel Antiangiogenic Agent KR‐31831 in Rat Plasma by Liquid Chromatography‐Tandem Mass Spectrometry

ABSTRACT

A liquid chromatography‐tandem mass spectrometric (LC/MS/MS) method was developed for the determination of a new anti‐angiogenic drug KR‐31831 in rat plasma. KR‐31831 and internal standard, KR‐31543 were extracted from rat plasma with dichloromethane at basic pH. A reverse‐phase LC separation was performed on Luna C8 column with the mixture of acetonitrile‐ammonium formate (10 mM, pH 4.5) (67:33, v/v) as mobile phase. The detection of analytes was performed using an electrospray ionization tandem mass spectrometry in the multiple‐reaction‐monitoring mode. The standard curve was linear (r = 0.999) over the concentration range of 1.0–500 ng/mL. The coefficient of variation of intra‐ and inter‐assay ranged from 0.8–3.9% and 1.4–3.9%, respectively. The recoveries of KR‐31831 ranged from 80.9% to 86.7%, with that of KR‐31543 (internal standard) being 99.2 ± 2.7%. The lower limits of quantification for KR‐31831 was 1.0 ng/mL using 100 µL plasma sample. This method was applied to the pharmacokinetic study of KR‐31831 in rats.

Keywords:

• KR‐31831
• Plasma
• LC/MS/MS
• Angiogenesis

ACKNOWLEDGMENT

This work was partially supported by the Project from the Center for Biological Modulators (CBM‐02‐B‐8), Ministry of Science and Technology, Republic of Korea.

Notes

Note: —, Not assayed.