Tissues distribution of R-(-)- and S-(+)-m-nisoldipine after single enantiomer administration in rats.
Rapid, sensitive, and selective high-performance liquid chromatography methods were developed and validated for determination of m-nisoldipine enantiomers in rat tissues. All of the samples were prepared based on a simple and efficient liquid-liquid extraction method. After validating that no racemation occurred by ULTRON ES-OVM (Japan), m-nisoldipine enantiomers were determined, respectively, on a reverse-phase C(18) column (5 microm, 250 x 4.6 mm). This method was applied to study tissue distribution of m-nisoldipine enantiomers in rats after a single administration of m-nisoldipine enantiomers. By the two-sample t test, there were basically no significant differences between the two enantiomers in each tissue ( p > .05), which indicates that they may have the same potency in rats. In small intestine, lung, liver, and spleen, the concentrations of R-(-)- and S-(+)-m-nisoldipine were high at 30 and 150 min than that at 90 min, which showed that m-nisoldipine enantiomers may have the phenomenon of hepatoenteral circulation. A small quantity of the prototype of R-(-)- and S-(+)-m-nisoldipine in brain showed that they can cross the blood-brain barrier to arrive at the brain tissue. The high quantity of distribution in lung and brain implied that the lipophilicity of the drug was powerful.
Li
Min
M
Department of Pharmaceutical Analysis, School of Pharmacy, Hebei Medical University, Shijiazhuang, P.R. China.
Wang
Qiao
Q
Wang
Chunying
C
Jing
Xiujuan
X
Duan
Kunfeng
K
Chen
Xiang'ai
X
Xu
Lei
L
Tian
Yaping
Y
Zhang
Lantong
L
Du
Yumin
Y
Zhang
Xiaowei
X
Sheng
Xiaona
X
D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D008297:Male; D015737:Nisoldipine / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D014018:Tissue Distribution
D002121:Calcium Channel Blockers; D015737:Nisoldipine