A rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was established for the determination of sarpogrelate in human plasma. One-step protein precipitation with acetonitrile was used to extract the analytes from the plasma. Sarpogrelate and tramadol (internal standard, I.S.) were separated on a Venusil MP-C(18) column within 1.7 min, using acetonitrile:ammonium acetate (10 mM, pH 6.8) (55:45, v/v) as mobile phase at a flow rate of 1.2 mL/min with an approximately 1:1 split entering the mass spectrometer. Detection was performed on electrospray positive ionization mass spectrometry by multiple reaction monitoring of the transitions of sarpogrelate at m/z 430.3-->135.3 and of I.S. at m/z 264.1-->58.0. The assay was validated over the concentration range of 1-1000 ng/mL with a lower limit of quantitation (LLOQ) of 1 ng/mL using 50 microL of plasma. The intra- and inter-day precision (relative standard deviation, R.S.D.) were <or=6.4% and <or=5.4%, respectively, with accuracy (relative error, R.E.) in the range 0.5-3.6%. The method was successfully applied to a pharmacokinetic and bioequivalence study enrolling 22 Chinese volunteers administered sarpogrelate tablets.
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