Enantiomers of triclabendazole sulfoxide: Analytical and semipreparative HPLC separation, absolute configuration assignment, and transformation into sodium salt.
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, 12.5mg of racemic sample were resolved in a single chromatographic run within 15min. 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.
Centro nazionale per il controllo e la valutazione dei farmaci, Istituto Superiore di Sanità, Viale Regina Elena 299, I-00161 Rome, Italy.
Rosella
R
Ferretti
Dipartimento di Farmacia, Università "G. D'Annunzio" di Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy.
Simone
S
Carradori
Dipartimento di Chimica e Tecnologie del Farmaco, "Sapienza" Università di Roma, P.le A. Moro 5, 00185 Rome, Italy.
Paolo
P
Guglielmi
Dipartimento di Chimica e Tecnologie del Farmaco, "Sapienza" Università di Roma, P.le A. Moro 5, 00185 Rome, Italy.
Marco
M
Pierini
Dipartimento di Malattie Infettive, Istituto Superiore di Sanità, Viale Regina Elena 299, I-00161 Rome, Italy; World Health Organization Collaborating Centre for the Epidemiology, Detection and Control of Cystic and Alveolar Echinococcosis (in Animals and Humans), Istituto Superiore di Sanità, Viale Regina Elena 299, I-00161 Rome, Italy.
Adriano
A
Casulli
Centro nazionale per il controllo e la valutazione dei farmaci, Istituto Superiore di Sanità, Viale Regina Elena 299, I-00161 Rome, Italy. Electronic address: roberto.cirilli@iss.it.
Roberto
R
Cirilli
D001562:Benzimidazoles / Q000032:analysis*; D002851:Chromatography, High Pressure Liquid; D006586:Hexanes; D012964:Sodium; D013237:Stereoisomerism; D013454:Sulfoxides / Q000032:analysis*; D000077682:Triclabendazole
D001562:Benzimidazoles; D006586:Hexanes; D013454:Sulfoxides; C026385:n-hexane; D000077682:Triclabendazole; D012964:Sodium; C085104:triclabendazole sulfoxide
Absolute configuration assignment; Chiralpak AS-H; Chiralpak IF-3; Enantiomers; Parasites; Triclabendazole sulfoxide