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) |
|---|---|
| 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 |
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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 journal › Article
}
TY - JOUR
T1 - HPLC/MS/MS analysis of 3-carbamyl-4-methylpyrrole analog MNP001, a highly potent antihypertensive agent, in rat plasma
AU - Xia, Binfeng
AU - Wang, Ting
AU - Fox, Laura M.
AU - Wang, Desuo
PY - 2009/7/1
Y1 - 2009/7/1
N2 - 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.
AB - 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.
KW - Antihypertensive
KW - HPLC/MS/MS
KW - MNP001
KW - NP06
KW - Validation
UR - http://www.scopus.com/inward/record.url?scp=67049086737&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=67049086737&partnerID=8YFLogxK
U2 - 10.1016/j.jchromb.2009.05.011
DO - 10.1016/j.jchromb.2009.05.011
M3 - Article
C2 - 19487166
AN - SCOPUS:67049086737
VL - 877
SP - 1867
EP - 1872
JO - Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
JF - Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
SN - 1570-0232
IS - 20-21
ER -