Summary
A 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-methyl-N-(trimethylsilyl)trifluoroacetamide to form an O-silyl ether, followed by subsequent chiral derivatization with (−)-α-methoxy-α-(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·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 healthy volunteers dosed with racemic metoprolol tartrate.
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Murthy, S.S.; Shetty, H.U.; Nelson, W.L.; Jackson P.R.; Lennard, M.S.Biochem. Pharmacol. 1990,40, 1637–644.
Nathanson, J.A.J. Pharmacol. Exp. Ther. 1988,245, 94–101.
Rauch, P.; Puttmann, M.; Oesch, F.; Okamoto Y.; Robertson, L.W.Biochem. Pharmacol. 1987,36, 4355–4359.
Rutledge, D.R.; Garrick, C.J. Chromatogr. 1989,497, 181–190.
Gyllenhaal, O.; Vessmann, J.J. Chromatogr. 1988,435, 259–269.
Lanchote, V.L.; Bonato, P.S.; Cerqueira, P.M.; Pereira, V.A.; Cesarino, E.J.J. Chromatogr. B 2000,738, 27–37.
Kim, K.H.; Kim, H.J.; Kang, J.S.; Mar, W.C.J. Pharm. Biomed. Anal. 2000,22, 377–384.
Mangani, F.; Luck, G.; Fraudeau, C.; Vérette, E.J. Chromatogr. A 1997,762, 235–384.
Persson, B.-A.; Balmér, K.; Lagerström, P.-O.; Schill, G.J. Chromatogr. A 1990,500, 629–636.
Lim, H.K.; Linh, P.T.; Hong, C.H.; Kim, K.H.; Kang, J.S.J. Chromatogr. B 2001,755, 259–264.
Shin, H.S.; Donike, M.Anal. Chem. 1996,68, 3015–3020.
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Kim, K.H., Lee, J.H., Ko, M.Y. et al. Determination of metoprolol enantiomers in human urine by GC-MS using (−)-α-methoxy-α-(trifluoromethyl)phenylacetyl chloride as a chiral derivatizing agent. Chromatographia 55, 81–85 (2002). https://doi.org/10.1007/BF02492319
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DOI: https://doi.org/10.1007/BF02492319