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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

✍ Scribed by Shinsuke Inagaki; Sayuri Taniguchi; Haruo Hirashima; Tatsuya Higashi; Jun Zhe Min; Ruri Kikura-Hanajiri; Yukihiro Goda; Toshimasa Toyo'oka


Publisher
John Wiley and Sons
Year
2010
Tongue
English
Weight
251 KB
Volume
33
Category
Article
ISSN
1615-9306

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✦ Synopsis


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 (R~s~)=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).