Chiral separation of β-blockers after derivatization with (-)-α-Methoxy-α-(trifluoromethyl)phenylacetyl chloride by gas chromatography

Abstract

Gas chromatographic method was investigated for the chiral separation of several beta-blockers(atenolol, betaxolol, bisoprolol, metoprolol and pindolol) using (-)-alpha-methoxy-alpha-(trifluoromethyl)phenylacetyl chloride as a chiral derivatizing agent for amino group. Prior to N-acylation, hydroxyl group was converted into O-silyl ethers by react with N-methyl-N-(trimethylsilyl)trifluoroacetamide. The reaction was selective and rapid and the diastereomeric derivatives were well separated by capillary gas chromatography. (R)-isomers were eluted faster than (S)-isomers when (-)-alpha-methoxy-alpha-(trifluoromethyl)phenylacetyl chloride was used as the chiral derivatizing agent. But in the opposite sequence when (+)-alpha-methoxy-alpha-(trifluoromethyl)phenylacetyl chloride was used. No racemization was found during the reaction.

Simultaneous determination of metoprolol succinate and amlodipine besylate in human plasma by liquid chromatography–tandem mass spectrometry method and its application in bioequivalence study

“…HPLC [5,[10][11][12][13][14][15], LC-MS [16][17][18][19], GC-MS [20,21] has been reported. Enantiomers of MPS have also been determined by HPLC [22][23][24]. Usually in a clinical study, large numbers of samples are collected.…”

“…Previously reported methods either had long retention time (10-15 min) or suffered from low sensitivity and in some cases required large sample injection volumes (100 l). There are various methods reported for the determination of MPS [5,[10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] and AM [4][5][6][7][8][9] separately. To the best of our knowledge, there is no method reported in the literature for the simultaneous determination of these analytes by LC-MS/MS.…”

Liquid chromatographic–electrospray tandem mass spectrometric determination of bisoprolol in human plasma

“…Prior to the prevalent use of LC-MS techniques, various analytical methods, such as capillary electrophoresis (Awadallah et al, 2003), gas chromatography (Kim et al, 2001) and HPLC with an ultraviolet (Zhang et al, 2003;Ruiz-Angel et al, 2002;Modamio et al, 1996), fluorescence (Buhring and Garbe, 1986;Eastwood et al, 1990;Suzuki et al, 1993) or diode array detector (Caudron et al, 2004), have been developed to determine bisoprolol in formulation and biological samples.…”

Liquid chromatography tandem mass spectrometry method for simultaneous determination of metoprolol tartrate and ramipril in human plasma

“…Determination of metoprolol, viz HPLC [11][12][13][14][15][16], LC-MS [17][18][19][20], GC-MS [21][22] has been reported. Enantiomers of metoprolol have also been determined by HPLC [23][24][25].…”