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 language | English (US) |
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Pages (from-to) | 1867-1872 |
Number of pages | 6 |
Journal | Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences |
Volume | 877 |
Issue number | 20-21 |
DOIs | |
State | Published - Jul 1 2009 |
Externally published | Yes |
Keywords
- Antihypertensive
- HPLC/MS/MS
- MNP001
- NP06
- Validation
ASJC Scopus subject areas
- Analytical Chemistry
- Biochemistry
- Clinical Biochemistry
- Cell Biology