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

Binfeng Xia, Ting Wang, Laura M. Fox, Desuo Wang

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1867-1872
Number of pages6
JournalJournal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
Volume877
Issue number20-21
DOIs
StatePublished - Jul 1 2009
Externally publishedYes

Fingerprint

Type 4 Cyclic Nucleotide Phosphodiesterase
Antihypertensive Agents
Rats
Pyrroles
High Pressure Liquid Chromatography
Plasmas
Pharmacodynamics
L-Type Calcium Channels
Pharmacokinetics
Blood pressure
High performance liquid chromatography
Tandem Mass Spectrometry
Calibration
Mass spectrometry
Animals
Heart Rate
Blood Pressure
MNP 001

Keywords

  • Antihypertensive
  • HPLC/MS/MS
  • MNP001
  • NP06
  • Validation

ASJC Scopus subject areas

  • Biochemistry
  • Analytical Chemistry
  • Cell Biology
  • Clinical Biochemistry

Cite this

HPLC/MS/MS analysis of 3-carbamyl-4-methylpyrrole analog MNP001, a highly potent antihypertensive agent, in rat plasma. / Xia, Binfeng; Wang, Ting; Fox, Laura M.; Wang, Desuo.

In: Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, Vol. 877, No. 20-21, 01.07.2009, p. 1867-1872.

Research output: Contribution to journalArticle

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