RESUMO
Objective To detect the plasma concentrations of daptomycin in the left ventricle and right ventricle of rats by high-performance liquid chromatography-mass spectrometry(LC-MS/MS), and evaluate the therapeutic effect of daptomycin on left ventricular endocarditis. Methods Thirty-five healthy Sprague-Dawley (SD) rats were divided into a normal saline group (5 rats) and a daptomycin group (30 rats) according to the random number table method. The daptomycin group was subdivided into 6 subgroups according to the times of blood collection (0.25, 0.5, 1, 2, 4, 8 hours), with 5 rats in each subgroup. The normal saline group was given 4 mL/kg normal saline; the daptomycin group was injected with 50 mg/kg daptomycin into the tail vein. The blood samples from left ventricle and right ventricle were extracted at the corresponding time points, the plasma concentrations of daptomycin group were determined by high performance liquid chromatography-mass spectrometry (HPLC-MS) and the differences of left ventricular and right ventricular plasma concentrations were compared at different time points. The plasma in normal saline group was the blank plasma that was used for HPLC-MS methodological evaluation. Results There were no statistical significant differences between the left ventricle and right ventricle in plasma concentrations of daptomycin at 0.25, 0.5, 1, 2, 4, and 8 hours after administration (g/L: 2.67±0.30 vs. 2.77±0.31, 1.77±1.27 vs. 1.64±0.55, 1.35±0.40 vs. 1.36±0.41, 0.97±0.07 vs. 0.92±0.09, 0.73±0.16 vs. 0.65±0.18, 0.07±0.06 vs. 0.06±0.05, respectively all P > 0.05). Conclusion There are no significant differences between the left ventricle and right ventricle in plasma concentrations of daptomycin. It is speculated that daptomycin may have the same therapeutic effect on left endocarditis.
RESUMO
Objective To establish an LC-MS/MS method for the detection of landiolol concentration in human blood.Methods After pretreatment with neostigmine and a deproteinization procedure, landiolol and the internal standard venlafaxine were eluted isocratically using a mobile phase consisting of acetonitrile and 10 mmoL·L-1 ammonium acetate with 0. 1% formic acid in a ratio of 3664 ( V/V ) . Separation of the respective compounds was achieved on a Waters XTerra? RP18 column (150 mmí4. 6 mm,5 μm). Quantitative analysis of landiolol was conducted by a triple-quadrupole mass spectrometer with positive-electrospray ionization source,monitored under a multiple reaction monitoring ( MRM) mode. The extracted ions monitored following MRM transitions were m/z 510. 5→423. 1 for landiolol and m/z 278. 2→215. 1 for the internal standard venlafaxine. ResultsThe calibration curve of landiolol in human blood showed good linear relationship in the range of 1. 010-2 020 μg·L-1 . The lower limit of quantitation was 1. 010 μg · L-1 . The RSD of within-day and between-day precision was less than 6. 5% and 4. 8%, respectively. The recovery rate was 92. 6%-100. 9%. Conclusion The method is proven to be simple,rapid and reliable,and can be applied to study the pharmacokinetics of landiolol hydrochloride in healthy Chinese volunteers.