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.
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).
Inagaki
Shinsuke
S
Laboratory of Analytical and Bio-Analytical Chemistry, School of Pharmaceutical Sciences, and Global COE Program, University of Shizuoka, Shizuoka, Japan.
Taniguchi
Sayuri
S
Hirashima
Haruo
H
Higashi
Tatsuya
T
Min
Jun Zhe
JZ
Kikura-Hanajiri
Ruri
R
Goda
Yukihiro
Y
Toyo'oka
Toshimasa
T
D000284:Administration, Oral; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D005456:Fluorescent Dyes / Q000737:chemistry*; D008297:Male; D008774:Methylphenidate / Q000097:blood* / Q000737:chemistry*; D015394:Molecular Structure; D011759:Pyrrolidines / Q000097:blood* / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism
D005456:Fluorescent Dyes; D011759:Pyrrolidines; D008774:Methylphenidate