title: Enantioselective column coupled electrophoresis employing large bore capillaries hyphenated with tandem mass spectrometry for ultra-trace determination of chiral compounds in complex real samples.
abstract: A new multidimensional analytical approach for the ultra-trace determination of target chiral compounds in unpretreated complex real samples was developed in this work. The proposed analytical system provided high orthogonality due to on-line combination of three different methods (separation mechanisms), i.e. (1) isotachophoresis (ITP), (2) chiral capillary zone electrophoresis (chiral CZE), and (3) triple quadrupole mass spectrometry (QqQ MS). The ITP step, performed in a large bore capillary (800 μm), was utilized for the effective sample pretreatment (preconcentration and matrix clean-up) in a large injection volume (1-10 μL) enabling to obtain as low as ca. 80 pg/mL limits of detection for the target enantiomers in urine matrices. In the chiral CZE step, the different chiral selectors (neutral, ionizable, and permanently charged cyclodextrins) and buffer systems were tested in terms of enantioselectivity and influence on the MS detection response. The performance parameters of the optimized ITP - chiral CZE-QqQ MS method were evaluated according to the FDA guidance for bioanalytical method validation. Successful validation and application (enantioselective monitoring of renally eliminated pheniramine and its metabolite in human urine) highlighted great potential of this chiral approach in advanced enantioselective biomedical applications.
authors.affiliation: Department of Pharmaceutical Analysis and Nuclear Pharmacy, Faculty of Pharmacy, Comenius University in Bratislava, Bratislava, Slovak Republic.|Toxicological and Antidoping Center, Faculty of Pharmacy, Comenius University in Bratislava, Bratislava, Slovak Republic.
authors.forename: Juraj
authors.initials: J
authors.lastname: Piešťanský
authors.affiliation: Department of Pharmaceutical Analysis and Nuclear Pharmacy, Faculty of Pharmacy, Comenius University in Bratislava, Bratislava, Slovak Republic.|Toxicological and Antidoping Center, Faculty of Pharmacy, Comenius University in Bratislava, Bratislava, Slovak Republic.
authors.forename: Katarína
authors.initials: K
authors.lastname: Maráková
authors.affiliation: Villa Labeco spol. s r. o, Spišská Nová Ves, Slovak Republic.
authors.forename: Marián
authors.initials: M
authors.lastname: Kovaľ
authors.affiliation: Department of Pharmaceutical Analysis and Nuclear Pharmacy, Faculty of Pharmacy, Comenius University in Bratislava, Bratislava, Slovak Republic.
authors.forename: Emil
authors.initials: E
authors.lastname: Havránek
authors.affiliation: Department of Pharmaceutical Analysis and Nuclear Pharmacy, Faculty of Pharmacy, Comenius University in Bratislava, Bratislava, Slovak Republic.|Toxicological and Antidoping Center, Faculty of Pharmacy, Comenius University in Bratislava, Bratislava, Slovak Republic.
authors.forename: Peter
authors.initials: P
authors.lastname: Mikuš
mesh_terms: D019075:Electrophoresis, Capillary / Q000295:instrumentation / Q000379:methods*; D004867:Equipment Design; D005260:Female; D006801:Humans; D057230:Limit of Detection; D016014:Linear Models; D008297:Male; D008956:Models, Chemical; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000302:isolation & purification / Q000652:urine*; D015203:Reproducibility of Results; D013237:Stereoisomerism; D053719:Tandem Mass Spectrometry / Q000295:instrumentation / Q000379:methods*
chemical_list: D004364:Pharmaceutical Preparations
keywords: Capillary isotachophoresis; Chiral capillary zone electrophoresis; Drug enantiomer analysis; Hyphenation; Tandem mass spectrometry