title: Simultaneous determination of m-nisoldipine and its three metabolites in rat plasma by liquid chromatography-mass spectrometry.
abstract: A simple, sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous determination of m-nisoldipine and its three metabolites in rat plasma has been developed using nitrendipine as an internal standard (IS). Following liquid-liquid extraction, the analytes were separated using an isocratic mobile phase on a reverse phase C(18) column and analyzed by MS in the multiple reaction monitoring (MRM) mode. To avoid contamination by residual sample in the injection syringe, a special injection protocol was developed. We found that m-nisoldipine, metabolite M1 and IS could be ionized under positive or negative electrospray ionization conditions, whereas metabolite M and M2 could only be ionized in the positive mode. The mass spectrometry fragmentation pathways for these analytes are analyzed and discussed herein. The total analysis time required less than 5 min per sample. We employed this method successfully to study the metabolism of m-nisoldipine when it was orally administered to rats at a dose of 9 mg/kg. Three metabolites of m-nisoldipine and an unknown compound of molecular weight 386 were found for the first time in rat plasma. The concentration of the potentially active metabolite was approximately equal to its parent compound concentration.
authors.affiliation: Department of Pharmaceutical Analysis, School of Pharmacy, Hebei Medical University, Shijiazhuang 050017, China.
authors.forename: Dezhi
authors.initials: D
authors.lastname: Kong
authors.forename: Sanni
authors.initials: S
authors.lastname: Li
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Zhang
authors.forename: Jianmin
authors.initials: J
authors.lastname: Gu
authors.forename: Man
authors.initials: M
authors.lastname: Liu
authors.forename: Yan
authors.initials: Y
authors.lastname: Meng
authors.forename: Yan
authors.initials: Y
authors.lastname: Fu
authors.forename: Xiaojin
authors.initials: X
authors.lastname: La
authors.forename: Gangqiang
authors.initials: G
authors.lastname: Xue
authors.forename: Lantong
authors.initials: L
authors.lastname: Zhang
authors.forename: Qiao
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D008297:Male; D015394:Molecular Structure; D015737:Nisoldipine / Q000097:blood* / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D015737:Nisoldipine