TY - JOUR

T1 - Liquid-phase microextraction combined with capillary electrophoresis, a promising tool for the determination of chiral drugs in biological matrices

AU - Andersen, Solveig

AU - Halvorsen, Trine Grønhaug

AU - Pedersen-Bjergaard, Stig

AU - Rasmussen, Knut E.

PY - 2002/7/19

Y1 - 2002/7/19

N2 - A disposable device for liquid-phase microextraction (LPME) based on porous polypropylene hollow fibres has recently been introduced. In the present paper, LPME was combined with capillary electrophoresis (CE) and the combination was for the first time evaluated for chiral determination of drugs in biological matrices. The chiral antidepressant drug mianserin was selected as model compound. The mianserin enantiomers were extracted from 0.5 ml of plasma added internal standard and made alkaline with 0.25 ml of 2 M NaOH. The unionised analytes were extracted into di-n-hexyl ether impregnated in the pores of the hollow fibre, and into an acidic solution inside the hollow fibre. This resulted in a three-phase system where the extracts were aqueous, and hence directly compatible with the CE system. Efficient sample clean-up was seen and the extraction recovery was 80% for both enantiomers. Discrimination between the enantiomers in the extraction system was not observed. The limit of quantitation (S/N=10; 12.5 ng/ml for both enantiomers) and the limit of detection (S/N=3; 4 ng/ml for both enantiomers) were below the therapeutic range for mianserin. The method was validated and successfully applied to determine R- and S-mianserin in plasma samples from seven patients treated with mianserin, indicating that LPME-CE is a promising combination for analysis of racemic drugs present in low concentrations in biological matrices.

AB - A disposable device for liquid-phase microextraction (LPME) based on porous polypropylene hollow fibres has recently been introduced. In the present paper, LPME was combined with capillary electrophoresis (CE) and the combination was for the first time evaluated for chiral determination of drugs in biological matrices. The chiral antidepressant drug mianserin was selected as model compound. The mianserin enantiomers were extracted from 0.5 ml of plasma added internal standard and made alkaline with 0.25 ml of 2 M NaOH. The unionised analytes were extracted into di-n-hexyl ether impregnated in the pores of the hollow fibre, and into an acidic solution inside the hollow fibre. This resulted in a three-phase system where the extracts were aqueous, and hence directly compatible with the CE system. Efficient sample clean-up was seen and the extraction recovery was 80% for both enantiomers. Discrimination between the enantiomers in the extraction system was not observed. The limit of quantitation (S/N=10; 12.5 ng/ml for both enantiomers) and the limit of detection (S/N=3; 4 ng/ml for both enantiomers) were below the therapeutic range for mianserin. The method was validated and successfully applied to determine R- and S-mianserin in plasma samples from seven patients treated with mianserin, indicating that LPME-CE is a promising combination for analysis of racemic drugs present in low concentrations in biological matrices.

KW - Antidepressants

KW - Enantiomer separations

KW - Extraction methods

KW - Hollow fibres

KW - Liquid-phase microextraction

KW - Mianserin

UR - http://www.scopus.com/inward/record.url?scp=0037135005&partnerID=8YFLogxK

U2 - 10.1016/S0021-9673(02)00223-6

DO - 10.1016/S0021-9673(02)00223-6

M3 - Journal article

C2 - 12187985

AN - SCOPUS:0037135005

VL - 963

SP - 303

EP - 312

JO - Journal of Chromatography

JF - Journal of Chromatography

SN - 0301-4770

IS - 1-2

ER -