Stereoselective determination of trihexyphenidyl in human serum by LC-ESI-MS.
The antiparkinsonian drug trihexyphenidyl (THP) is currently manufactured and administered as a racemate. However, stereochemistry can play significant role in the drug's pharmacokinetics, biotransformation, metabolism, interaction with cellular and tissue components and overall effect on human body. It is necessary to consider such a drug as a mixture of two compounds (drug enantiomers), with their own effect on the human body. The present paper describes a simple and sensitive LC-MS method for the stereoselective determination of THP in human serum. In this study, the sample was prepared by a solid-phase extraction (SPE) procedure. The enantiomer separation was done using native beta-cyclodextrin stationary phase LC column. The combination of ESI-MS detection and SPE showed excellent sensitivity and selectivity of the method. The limits of detection of <0.1 ng/ml can be easily achieved, which is 7,000 times lower than the detection limits achievable by a UV detection method. The method has at least a 3-order of magnitude linear dynamic range for both enantiomers (concentrations up to 1,323 ng/ml were tested). This is 24 times wider than the therapeutic range of THP (peak THP plasma concentration of 55 ng/ml was previously reported). The recoveries of THP enantiomers from the human serum were > 95%.
Cápka
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Department of Chemistry, Cleveland State University, OH 44115, USA.
Xu
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Chen
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YH
D019342:Acetic Acid / Q000737:chemistry; D000978:Antiparkinson Agents / Q000032:analysis / Q000097:blood*; D002138:Calibration; D002853:Chromatography, Liquid / Q000379:methods*; D005021:Ethylamines / Q000737:chemistry; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D000432:Methanol / Q000737:chemistry; D013237:Stereoisomerism; D014282:Trihexyphenidyl / Q000032:analysis / Q000097:blood*
D000978:Antiparkinson Agents; D005021:Ethylamines; D014282:Trihexyphenidyl; D019342:Acetic Acid; C016162:triethylamine; D000432:Methanol