HPLC/MS/MS analysis of 3-carbamyl-4-methylpyrrole analog MNP001, a highly potent antihypertensive agent, in rat plasma Article

Xia, B, Wang, T, Fox, LM et al. (2009). HPLC/MS/MS analysis of 3-carbamyl-4-methylpyrrole analog MNP001, a highly potent antihypertensive agent, in rat plasma . JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES, 877(20-21), 1867-1872. 10.1016/j.jchromb.2009.05.011

cited authors

  • Xia, B; Wang, T; Fox, LM; Wang, D

authors

abstract

  • Chemically synthesized 3-carbamyl-4-methylpyrroles were characterized as a group of antihypertensive agents with dual-targeting mechanism to simultaneously inhibit type 4 phosphodiesterase (PDE4) and L-type calcium channels. A 5-butyl analog of the pyrrole family, MNP001, was found to have high potency in reducing animal blood pressure and heart rate. A method for measuring MNP001 using high performance liquid chromatography combined with tandem mass spectrometry (HPLC/MS/MS) was developed. The calibration curve for MNP001 showed good linearity with the value of correlation coefficient greater than 0.987 over the range of 0.25-500 ng/mL. The results for inter-day and intra-day precision as well as accuracy were acceptable according to the criteria established by FDA. The lower limit of quantification was 0.25 ng/mL. This method was quick, sensitive and sufficient for in vivo pharmacokinetic and pharmacodynamic studies on this novel antihypertensive pyrrole compound. © 2009 Elsevier B.V. All rights reserved.

publication date

  • July 1, 2009

Digital Object Identifier (DOI)

start page

  • 1867

end page

  • 1872

volume

  • 877

issue

  • 20-21