Résumé
OBJECTIVE: To establish a rapid column-switching-ultra high performance liquid chromatography method for determining meropenem concentration in human plasma. METHODS: Meropenem plasma samples were diluted by internal standard aqueous solution (doxofylline), filtrated by microporous membrane, and then extracted by on-line column-switching method. The samples were chromatographed on Waters Acquity UPLC@BEH-C18 column using gradient elution method (mobile phase A and extracting mobile phase C: methanol -0.05 mol·L-1 K2HPO4 (pH 7.0) 5:95; mobile phase B: methanol). The maximum absorption wavelength of meropenem was 299 nm. The column temperature were 35°C. The meropenem concentration was calculated by internal standard method and external standard method, respectively. The results of the two methods were compared by paired t-test using SPSS statistical software. RESULTS: The liner range of the calibration curve for meropenem was 0.67-86.00 mg·L-1 (r=0.9999). The method recovery was (93.59±1.15)%-(99.21±4.06)% and extraction recovery was above 85.0%, relative standard deviation was below 5.0%. The SPSS statistic results indicated there was no significant difference between the concentrations calculated by the two methods and existed good correlation. The transformed equation is ρInternal=1.039ρExternal-0.468 (r=0.9970). CONCLUSION: On-line column-switching method is used and it is proved to be rapid, sensitive and suitable for therapeutic drug monitoring and pharmacokinetic investigation of meropenem in human plasma.