Determination of daptomycin by UPLC-MS/MS and its pharmacokinetic eva-luation in critically ill patients

A sensitive, selective and simple liquid chromatography tandem mass spectrometry(UPLC-MS/MS)method was developed for determining of daptomycinin human plasma and effluent. The analyte was extracted from plasma samples by SPE method, separated through a Phenomenex Kinetex C₁₈ column(50 mm×2. 1 mm, 1. 7 μm)using isocratic mobile phase consisting of 0. 1% formic acid-acetonitile(75 ∶25), and analyzed by electro-spray ionization(ESI). The precursor to product ion transitions of m/z 810. 9→159. 1 and m/z 286. 2→217. 2 were used to measure daptomycinand the internal standard, respectively. The method was validated over a concentration range(plasma: 1-200 μg/mL, effulent: 0. 005-20 μg/mL). The intra- and inter-day precision values were less than 10% and accuracy values 90%-110%. The stability of daptomycinin human plasma and effluent under different storage conditions met the requirements of bioanalytical method. The concentration of daptomycin is significant lower in the septic shock patient, when give a dose of 6 mg/kg, the c_max and AUC_{0-24 h} of steady state decreased by 50% and 60% respectively; the increase in capillary permeability and interstitial oedema during sepsis and septic shock may enhance drug distribution. By the way, daptomycin can be cleared via continuous veno-venous hemofiltration(CVVH)for nearly 16%. In summary, on the treatment of continuous renal replacement therapy(CRRT)in patients with septic shock with daptomycin therapy, the suggested dose should be increased, and the drug monitoring should be carried on.