HPLC/MS/MS analysis of 3-carbamyl-4-methylpyrrole analog MNP001, a highly potent antihypertensive agent, in rat plasma.
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.
Xia
Binfeng
B
Department of Basic Pharmaceutical Sciences, South Carolina College of Pharmacy, University of South Carolina, Columbia, SC 29208, USA.
Wang
Ting
T
Fox
Laura M
LM
Wang
Desuo
D
D000818:Animals; D000959:Antihypertensive Agents / Q000097:blood*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D010880:Piperidines / Q000032:analysis* / Q000493:pharmacokinetics; D011758:Pyrroles / Q000032:analysis / Q000097:blood* / Q000493:pharmacokinetics; D051381:Rats; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
D000959:Antihypertensive Agents; C542795:MNP 001; D010880:Piperidines; D011758:Pyrroles