Determination of zolmitriptan enantiomers in rat liver microsomes by chiral high performance liquid chromatography with fl uorescence detection.
A selective chiral high performance liquid chromatographic method was developed and validated to separate and quantify the enantiomers of a new potent selective 5-HT(1B/1D) receptor partial agonist, S-zolmitriptan, and its antipode in rat liver microsomes induced with beta-naphtho flavone. S- and R-zolmitriptan were extracted from rat hepatic microsomal incubates with chloroform/isopropanol (75:25, v/v), and were separated on a narrow-bore enantioselective normal phase Chiralpak AD-H column (250 x 0.46 mm) with hexane-isopropanol-triethylamine (72/28/0.25, v/v/v) as mobile phase and fluorescence detection with emission at 350 nm and excitation at 291 nm. The calibration curves were linear for R- and S-zolmitriptan concentration over the range 0.1-5.0 microg/mL (r = 0.9996 and 0.9999), and the limits of quantitation were 0.1 microg/mL. The metabolism and interaction of the enantiomers of zolmitriptan in treated hepatic microsomes were investigated using chiral HPLC. There was significant difference between the disposition of the S- and R-zolmitriptan when racemic zolmitriptan or single enantiomers of zolmitriptan were incubated for 5, 10 and 20 min, suggesting that the metabolism of zolmitriptan in rat liver microsomes is enantioselective. In addition, there was also a significant difference between the IC(50) of R- to S-zolmitriptan and S- to R-zolmitriptan (IC(50S/R)/IC(50R/S) = 45.2). This indicated that the disposition process favored the S-form of zolmitriptan.
Department of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences, Zhejiang University, 353 Yan'an Road, Hangzhou, Zhejiang 310031, People's Republic of China.
Lushan
L
Yu
Tongwei
T
Yao
Shaoqing
S
Ni
Su
S
Zeng
D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005453:Fluorescence; D008297:Male; D008862:Microsomes, Liver / Q000737:chemistry* / Q000378:metabolism; D023303:Oxazolidinones / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D014363:Tryptamines
D023303:Oxazolidinones; D014363:Tryptamines; C089750:zolmitriptan