Determination of metoprolol enantiomers in human urine by GC-MS using (−)-α-methoxy-α-(trifluoromethyl)phenylacetyl chloride as a chiral derivatizing agent

Abstract

Key WordsGas chromatography -mass spectrometry Chiral separation Derivatization Metoprolol Urine samples S u m m a r yA method for the assay of R-(+)-and S-(-)-metoprolol in human urine has been developed using gas chromatography-mass spectrometry. The method involved purification by liquid-liquid extraction and derivatization with N-methyI-N-(trimethylsilyl)trifluoroacetamide to form an O-silyl ether, followed by subsequent chiral derivatization with (-)-~-methoxy-~-(trifluoromethyl)phenylacetyl chloride to form diastereomeric amide. The reaction was rapid and the diastereomeric derivatives were well resolved. Quantitation was performed by selected-ion monitoring of fragment ions of the diastereomers in electron impact ionization mode. No racemization was found during the reaction. The detection limit was 0.5 ng 9 mL 1. The intra-day variation ranged between 0.38 and 7.86% in relation to the measured concentration and inter-day variation was 2.26-8.06%. The method has been applied to the determination of R-(+)-and S-(-)-metoprolol in human urine from healthyvolunteers dosed with racemic metoproIol tartrate.Methods involving gas chromatography [5], high performance liquid chromatography [4,6,7,8,9] and capillary electrophoresis [10] have been developed for the quantitation of metoprolol enantiomers in biological samples. Shin [11] has described the stereospecific derivatization of amphetamine, phenol alkylamine and hydroxyamines and quantitation of the enantiomers by capillary GC-MS.This paper describes the O-silylation of the hydroxyl group of metoprolol using N-methyl-N-(trimethylsilyl) trifluoroacetamide(MSTFA) as a silylating reagent and the N-acylation of the amino group using ( )-e~-methoxy-e~-(trifluoromethyl)-phenylacetyl chloride(()-MTPA-C1) as a chiral derivatizing agent. This is followed by enantioselective determination of the metoprolol derivative in human urine by gas chromatography mass spectrometry with selected-ion monitoring.

Simultaneous determination of metoprolol succinate and amlodipine besylate in pharmaceutical dosage form by HPLC

“…USP 2006 describes an HPLC method for determination of MS as extended release tablets [3]. Few HPLC methods are reported in the literature for the simultaneous determination of some antihypertensive drugs from pharmaceutical dosage forms [4][5][6][7][8][9][10][11]. So far, to our present knowledge, no HPLC method is reported for the simultaneous determination of metoprolol succinate and amlodipine besylate in dosage forms.…”

Determination of metoprolol enantiomers in human plasma and saliva samples utilizing microextraction by packed sorbent and liquid chromatography–tandem mass spectrometry

“…Several methods have been reported for enantioselective determination of metoprolol in biological samples using different analytical techniques, such as liquid chromatography tandem mass spectrometry (LC-MS/MS) (Bae et al, 2014;Cerqueira et al, 2003;Jensen et al, 2008;Liang et al, 2010;Sharma et al, 2014), LC-UV (Ali et al, 2011;Iram and Shobha Rani, 2015;Lanchote et al, 2000), LC with fluorescence detection (Boralli et al, 2005;Cerqueira et al, 2003;Mistry et al, 2001), gas chromatography coupled to mass spectrometry (GC-MS) (Kim et al, 2002) and capillary electrophoresis (Lim et al, 2001). Several methods have been reported for enantioselective determination of metoprolol in biological samples using different analytical techniques, such as liquid chromatography tandem mass spectrometry (LC-MS/MS) (Bae et al, 2014;Cerqueira et al, 2003;Jensen et al, 2008;Liang et al, 2010;Sharma et al, 2014), LC-UV (Ali et al, 2011;Iram and Shobha Rani, 2015;Lanchote et al, 2000), LC with fluorescence detection (Boralli et al, 2005;Cerqueira et al, 2003;Mistry et al, 2001), gas chromatography coupled to mass spectrometry (GC-MS) (Kim et al, 2002) and capillary electrophoresis (Lim et al, 2001).…”

Enantiomeric Separation of Basic Drugs with Partially Filled Serum Albumin as Chiral Selector in Capillary Electrophoresis

“…1 The methods used for chiral separation include gas chromatography, [2][3][4] high performance liquid chromatography, [5][6][7][8] and capillary electrophoresis (CE). [9][10][11] Among these methods, CE has become one of the most powerful methods because of its high separation efficiency, rapid analysis ability and low reagent consumption.…”