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

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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.

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Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences





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This article was published in Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, Volume 877, Issue 20-21, Pages 1867-1872.

The published version is available at http://dx.doi.org/10.1016/j.jchromb.2009.05.011.

Copyright © 2009 Scopus.

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