Separation, isolation and stereochemical assignment of imazalil enantiomers and their quantitation in an in vitro toxicity test

TY - JOUR

T1 - Separation, isolation and stereochemical assignment of imazalil enantiomers and their quantitation in an in vitro toxicity test

AU - Casas, Mònica Escolà

AU - Kretschmann, Andreas Christopher

AU - Andernach, Lars

AU - Opatz, Till

AU - Bester, Kai

N1 - Copyright © 2016 Elsevier B.V. All rights reserved.

PY - 2016/6/24

Y1 - 2016/6/24

N2 - A simple method for the separation of the enantiomers of the fungicide imazalil was developed. Racemic imazalil was separated into its enantiomers with an enantiomeric purity of 99% using HPLC-UV with an enantioselective column (permethylated cyclodextrin) operated in reversed phase mode (water with 0.2% trimethylamine and 0.08% acetic acid and methanol). The absolute configuration of the separated enantiomers was assigned and unequivocally confirmed by optical rotation as well as by vibrational circular dichroism (VCD) and electronic circular dichroism (ECD) combined with ab-initio calculations. The same enantioselective column was also used to develop an HPLC–MS/MS method for the quantification of imazalil enantiomers. The HPLC–MS/MS method reached limits of quantification (LOQs) of 0.025 mg/mL with 5 μL injections. This method was used to verify imazalil concentrations and enantiomeric fractions in samples from an in vitro test on effects on human steroidogenesis (H295R steroidogenesis assay). The quantification verified the stability of the enantiomers of imazalil during the in vitro tests.

AB - A simple method for the separation of the enantiomers of the fungicide imazalil was developed. Racemic imazalil was separated into its enantiomers with an enantiomeric purity of 99% using HPLC-UV with an enantioselective column (permethylated cyclodextrin) operated in reversed phase mode (water with 0.2% trimethylamine and 0.08% acetic acid and methanol). The absolute configuration of the separated enantiomers was assigned and unequivocally confirmed by optical rotation as well as by vibrational circular dichroism (VCD) and electronic circular dichroism (ECD) combined with ab-initio calculations. The same enantioselective column was also used to develop an HPLC–MS/MS method for the quantification of imazalil enantiomers. The HPLC–MS/MS method reached limits of quantification (LOQs) of 0.025 mg/mL with 5 μL injections. This method was used to verify imazalil concentrations and enantiomeric fractions in samples from an in vitro test on effects on human steroidogenesis (H295R steroidogenesis assay). The quantification verified the stability of the enantiomers of imazalil during the in vitro tests.

KW - Journal Article

U2 - 10.1016/j.chroma.2016.05.008

DO - 10.1016/j.chroma.2016.05.008

M3 - Journal article

C2 - 27234843

SN - 0021-9673

VL - 1452

SP - 116

EP - 120

JO - Journal of Chromatography A

JF - Journal of Chromatography A

ER -