HPLC enantioseparation of α,α‐diphenyl‐2‐pyrrolidinemethanol and methylphenidate using a chiral fluorescent derivatization reagent and its application to the analysis of rat plasma |
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| Authors: | Shinsuke Inagaki Sayuri Taniguchi Haruo Hirashima Tatsuya Higashi Jun Zhe Min Ruri Kikura‐Hanajiri Yukihiro Goda Toshimasa Toyo'oka |
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| Affiliation: | 1. Laboratory of Analytical and Bio‐Analytical Chemistry, School of Pharmaceutical Sciences, and Global COE Program, University of Shizuoka, Shizuoka, Japan;2. Division of Pharmacognosy, Phytochemistry and Narcotics, National Institute of Health Sciences, Tokyo, Japan |
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| Abstract: | Enantioseparation of α,α‐diphenyl‐2‐pyrrolidinemethanol (D2PM) and methylphenidate (MPH; Ritalin®) using (R)‐(?)‐4‐(N,N‐dimethylaminosulfonyl)‐7‐(3‐isothiocyanatopyrrolidin‐1‐yl)‐2,1,3‐benzoxadiazole as the chiral derivatization reagent has been achieved for the first time, and a simple, reliable detection method using HPLC with fluorescence detection has been developed. D2PM and MPH have been derivatized with (R)‐(?)‐4‐(N,N‐dimethylaminosulfonyl)‐7‐(3‐isothiocyanatopyrrolidin‐1‐yl)‐2,1,3‐benzoxadiazole at 55°C for 15 min. The derivatives of D2PM and MPH have been separated, completely and rapidly, using a reversed‐phase system within 16 min (resolution factor (Rs)=1.60 and 2.53, respectively). The detection limits of (R)‐ and (S)‐D2PM were found to be 6.8 and 13 ng/mL, respectively, and those of D ‐ and L ‐threo‐MPH were 61 and 66 ng/mL, respectively (S/N=3). The proposed method was successfully applied to the analysis of rat plasma, where the rats were separately dosed with D2PM and MPH (Ritalin). |
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| Keywords: | α ,α ‐Diphenyl‐2‐pyrrolidinemethanol Enantioseparation Fluorescence detection HPLC Methylphenidate |
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