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

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).

Quantitative Analysis of Drugs in Biological Matrices by HPLC Hyphenated to Fluorescence Detection

“…The LLOQ was 40 ng/ml for each isomer. In 2010, Inagaki et al [90] reported the enantioseparation of two compounds: α, α-diphenyl-2-pyrrodilinemethanol (D2PM) and methylphenidate (MPH), quantified in rat plasma. The first of these is a phenethylamine analog, potentially addictive, that causes stimulation of the central nervous system or is a hallucinogen.…”

Stereo‐specific LC and LC‐MS bioassays of antidepressants and psychotics

“…Inagaki et al . () performed enantioseparation of α , α ‐diphenyl‐2‐pyrrolidinemethanol (D2PM) and MPH using ( R )‐(−)‐4‐( N , N ‐dimethylaminosulfonyl)‐7‐(3‐isothiocyanatopyrrolidin‐1‐yl)‐2,1,3‐benzoxadiazole as a chiral derivatization reagent for the first time. Protein precipitation coupled with LC with fluorescence detection was used.…”

Recent advances in development and application of derivatization reagents having a benzofurazan structure: a brief overview

“…( R )‐(+)‐NBD‐Pro‐COCl [( R )‐(+)‐4‐nitro‐7‐(2‐chloroformylpyrrolidin‐1‐yl)‐2,1,3‐benzoxadiazole] was used for the analysis of chiral amine, fluoxetine enantiomers (Higashi et al ., ). ( R )‐(−)‐DBD‐Py‐NCS [( R )‐(−)‐4‐( N , N ‐dimethylaminosulfonyl)‐7‐(3‐isothiocyanatopyrrolidin‐1‐yl)‐2,1,3‐benzoxadiazole] was used for the analysis of chiral amines such as D2PM ( α , α ‐diphenyl‐2‐pyrroridinemethanol), methylphenidate (Inagaki et al ., ), higenamine enantiomers (Hong et al ., ), tryptophan, kynurenine enantiomers (Iizuka et al ., , , ), d,l ‐amino acids (Min et al ., ) and illicit drugs (Inagaki et al ., ). DBD‐Apy [4‐( N , N ‐dimethylaminosulfonyl)‐7‐(3‐aminopyrrolidin‐1‐yl)‐2,1,3‐benzoxadiazole] was used for the analysis of chiral carboxylic acids such as dichlorprop (Inoue et al ., ), and ibuprofen, flurbiprofen and loxoprofen (Tsutsui et al ., ).…”