doi:10.1016/j.chroma.2005.11.078
Copyright © 2005 Elsevier B.V. All rights reserved.
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N-Menthoxycarbonylation combined with trimethylsilylation for enantioseparation of β-blockers by achiral dual-column gas chromatography
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Man-Jeong Paik, Duc-Toan Nguyen and Kyoung-Rae Kim
, 
Biometabolite Analysis Laboratory, College of Pharmacy, Sungkyunkwan University, Suwon 440-746, South Korea
Received 22 July 2005;
revised 8 November 2005;
accepted 23 November 2005.
Available online 19 December 2005.
Abstract
Solvent extractive two-phase menthoxycarbonyl (MnOC) derivatization was combined with trimethylsilyl (TMS) reaction for enantioseparation of β-blockers by gas chromatography employing achiral DB-5 and DB-17 dual-columns of different polarity. β-Blockers in alkaline solution were vortex-mixed with menthyl chloroformate present in dichloromethane to be extracted as diastereomeric N-MnOC derivatives. The subsequent O(N)-TMS reaction allowed complete enantioseparations of two β-blockers and partial separations of five as N-MnOC/O(N)-TMS derivatives in a single analysis. The temperature-programmed retention index sets were characteristic of each derivative, facilitating chiral discrimination of each enantiomer.
Keywords: β-Blockers; Enantioseparation; Menthoxycarbonylation; Dual-column gas chromatography
Fig. 1. Dual-enantiomeric profiles of seven racemic β-blockers as their diastereomeric N-(−)-menthoxycarbonyl/O(N)-trimethylsilyl derivatives separated on DB-5 MS and DB-17 MS dual-columns (both 15 m × 0.25 mm I.D., 0.25 μm film thickness). Helium flow rate was set to 1.0 ml/min with constant flow mode and samples (ca 1.0 μl) were injected in the splitless mode with purge delay time of 42 s. The oven was initially at 200 °C (1 min) and then programmed at 20 °C/min to 240 °C and finally at 2 °C/min to 290 °C (10 min). Peaks: (1) pronethalol; (2) metoprolol; (3) propranolol; (4) pindolol; (5) bisoprolol; (6) betaxolol; (7) carazolol; (IS) n-C32.
Fig. 2. Electron-impact mass spectra of pronethalol (A) as N-(−)-menthoxycarbonyl/mono-O-trimethylsilyl derivative, pindolol as N-(−)-menthoxycarbonyl/di-O(N) (B) and carazolol (C) as N-(−)-menthoxycarbonyl/di-O-trimethylsilyl derivatives obtained in the scanning mode at a rate of 0.99 scan/s with a mass range of 50–750 u.
Table 1.
Gas chromatographic data of seven β-blockers as diastereomeric N-(−)- menthoxycarbonyl/trimethylsilyl derivatives
a Resolution (
Rs) was the ratio of separation between two peaks to average width of the two peaks.
b Retention index (
I) measured in triplicate on DB-5 MS and DB-17 MS (both 15 m × 0.25 mm I.D., 0.25 μm film thickness) dual-columns programmed from 200 °C (1 min) to 240 °C at 20 °C/min, then to 290 °C at 2 °C/min (10 min). The helium flow rate was 1.0 ml/min in constant flow mode. Samples (ca 1.0 μl) were injected in the splitless mode with purge delay time of 42 s.
Table 2.
Mass spectral data of 15 β-blockers as N-(−)-menthoxycarbonyl/trimethylsilyl derivatives
a m/
z values with relative abundances of ions (%) in parentheses.
b Pindolol, carazolol, practolol, acebutolol and celiprolol as (−)-MnOC/di-TMS derivatives.
c Nadolol as (−)-MnOC/tri-TMS derivatives.
Corresponding author. Tel.: +82 31 290 7703; fax: +82 31 290 7723.
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