TY - JOUR
T1 - Enantiomers of triclabendazole sulfoxide
T2 - Analytical and semipreparative HPLC separation, absolute configuration assignment, and transformation into sodium salt
AU - Ferretti, Rosella
AU - Carradori, Simone
AU - Guglielmi, Paolo
AU - Pierini, Marco
AU - Casulli, Adriano
AU - Cirilli, Roberto
PY - 2017/6/5
Y1 - 2017/6/5
N2 - Direct HPLC separation of the enantiomers of triclabendazole sulfoxide (TCBZ-SO), which is the main metabolite of the anthelmintic drug triclabendazole, was carried out using the polysaccharide-based Chiralpak AS-H and Chiralpak IF-3 chiral stationary phases (CSPs). The chromatographic behaviour of both CSPs was evaluated and compared using normal-phase and reversed-phase eluents at different column temperatures. The eluent mixture of n-hexane-2-propanol-trifluoroacetic acid 70:30:0.1 (v/v/v) and a column temperature of 40 °C were identified as the best operational conditions to carry out semipreparative enantioseparations on a 1-cm I.D. AS-H column. Under these conditions, 12.5 mg of racemic sample were resolved in a single chromatographic run within 15 min. Comparison of calculated and experimental chiroptical properties provided the absolute configuration assignment at the sulfur atom. The salification of the isolated enantiomers of TCBZ-SO by reaction with sodium hydroxide solution produced water-soluble Na salts which are potentially useful in the development of new anthelmintic enantiomerically pure formulations.
AB - Direct HPLC separation of the enantiomers of triclabendazole sulfoxide (TCBZ-SO), which is the main metabolite of the anthelmintic drug triclabendazole, was carried out using the polysaccharide-based Chiralpak AS-H and Chiralpak IF-3 chiral stationary phases (CSPs). The chromatographic behaviour of both CSPs was evaluated and compared using normal-phase and reversed-phase eluents at different column temperatures. The eluent mixture of n-hexane-2-propanol-trifluoroacetic acid 70:30:0.1 (v/v/v) and a column temperature of 40 °C were identified as the best operational conditions to carry out semipreparative enantioseparations on a 1-cm I.D. AS-H column. Under these conditions, 12.5 mg of racemic sample were resolved in a single chromatographic run within 15 min. Comparison of calculated and experimental chiroptical properties provided the absolute configuration assignment at the sulfur atom. The salification of the isolated enantiomers of TCBZ-SO by reaction with sodium hydroxide solution produced water-soluble Na salts which are potentially useful in the development of new anthelmintic enantiomerically pure formulations.
KW - Absolute configuration assignment
KW - Chiralpak AS-H
KW - Chiralpak IF-3
KW - Enantiomers
KW - Parasites
KW - Triclabendazole sulfoxide
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U2 - 10.1016/j.jpba.2017.03.021
DO - 10.1016/j.jpba.2017.03.021
M3 - Article
C2 - 28340473
AN - SCOPUS:85015734029
VL - 140
SP - 38
EP - 44
JO - Journal of Pharmaceutical and Biomedical Analysis
JF - Journal of Pharmaceutical and Biomedical Analysis
SN - 0731-7085
ER -