摘要

A rapid, sensitive and reproducible LC-MS/MS method was developed and validated to determine iguratimod in human plasma. Sample preparation was achieved by protein precipitation with acetonitrile. Chromatographic separation was operated on an Ultimate (R) XB-C-18 column (2.1x50mm, 3.5m, Welch) with a flow rate of 0.400mL/min, using a gradient elution with acetonitrile and water which contained 2mm ammonium acetate and 0.1% formic acid as the mobile phase. The detection was performed on a Triple Quad 5500 mass spectrometer coupled with an electrospray ionization interface under positive-ion multiple reaction monitoring mode with the transition ion pairs of m/z 375.2347.1 for iguratimod and m/z 244.3185.0 for agomelatine (the internal standard), respectively. The method was linear over the range of 5.00-1500ng/mL with correlation coefficients 0.9978. The accuracy and precision of intra- and inter-day, dilution accuracy, recovery and stability of the method were all within the acceptable limits and no matrix effect or carryover was observed. As a result, the main pharmacokinetic parameters of iguratimod were as follows: C-max, 1074 +/- 373ng/mL; AUC(0-72), 13591 +/- 4557ngh/mL; AUC(0-), 13,712 +/- 4613ngh/mL; T-max, 3.29 +/- 1.23h; and t(1/2), 8.89 +/- 1.23h.

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