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Reversed‐Phase LC resolutions of chiral antiarrhythmic agents via derivatization with homochiral isothiocyanates
Author(s) -
Gal Joseph,
Meyerlehnert Sabine,
Desai Daksha M.
Publication year - 1990
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.530020107
Subject(s) - chemistry , derivatization , isothiocyanate , enantiomer , chromatography , enantioselective synthesis , mexiletine , stereochemistry , organic chemistry , high performance liquid chromatography , catalysis , medicine , anesthesia
The search for new antiarrhythmic agents has been intense, because the established drugs for the treatment of cardiac arrhythmias are neither uniformly effective nor well‐tolerated. Among the recently introduced new anti‐arrhythmic agents are tocainide (TOC), mexiletine (MEX), flecainide (FLE), and propafenone (PRO). Each of these drugs is a chiral amine used clinically as the racemic mixture. We have examined the high‐performance liquid chromatographic chiral resolution of the above four drugs via derivatization with homochiral derivatizing agents (HDAs). The amino functionality of the drugs was reacted with four homochiral isothiocyanates, 2,3,4,6‐tetra‐ O ‐acetyl‐β‐ D ‐glucopyranosyl isothiocyanate (TAGIT), (R)‐α‐methylbenzyl isothiocyanate (RAMBI), (S)‐1‐(1‐naphthyl)ethyl isothiocyanate (SNEIT), and (R)‐1‐(2‐naphthyl)ethyl isothiocyanate (RBEIT). Complete separation of the two peaks (resolution factor R = 1.5) was achieved with all four HDAs for TOC, with TAGIT, RBEIT, and RAMBI for MEX, with TAGIT and SNEIT for PRO, and only with TAGIT for FLE. SNEIT was used to develop analytical procedures for the determination of the enantiomeric composition of TOC in human urine and blood serum. The four HDAs offer several advantages over many other HDAs and should be useful in studies of enantioselective drug action and disposition.