Simultaneous determination of five antimicrobial agents in human plasma by LC-MS/MS and its clinical application in critically ill patients
OBJECTIVE To establish and validate a method of simultaneously detecting 5 common antibiotics in human plasma and implement therapeutic drug monitoring in 138 patients in intensive care unit(ICU).METHODS The plasma samples were precipitated with organic solvent and then examined by liquid chromatography-tandem mass spectrometry.Flow rate was 0.5 mL·min-1,column temperature 40 ℃ and analysis time 3.5 min.Electrospray ion source was scanned in positive/negative ion multiple reaction monitoring mode.RESULTS The linear relationship of voriconazole,linezolid,meropenem,cefo-perazone and sulbactam were decent at 0.2-40 μg·mL-1(r=0.997 4),0.5-100 μg·mL-1(r=0.999 4),0.5-100 μg·mL-1(r=0.999 4),1.5-300 μg·mL-1(r=0.993 6)and 1.5-300(r=0.997 9)μg·mL-1.The accuracy of lower quantification limit was 97.44％—100.72％with a precision of ≤9.35％and a within/between-run precision ≤13.88％.The recovery rates were 91.35％—106.08％and matrix effects 95.48％—107.42％.The relative deviation of dilution effect was＜15.00％.The stabil-ity of samples before and after treatment was decent under a variety of storage conditions.From November 2022 to March 2023,as for blood drug concentration test,the compliance rates of voriconazole,linezolid,meropenem,cefoperazone and sulbactam were 53.84％,27.27％,59.10％,20.00％and 25.00％.Basic profiles and blood drug concentrations of 20 critically ill patients were recorded.Under the same dosing regimen,great differences existed between individuals.CONCLUSION This simple and fast method offers decent profiles of accuracy,sensitivity and repeatability.It may be used for detecting the blood levels of 5 kinds of antibiotics in critically ill patients.It provides rationales for individualized dosing for patients with severe infection.
LC-MS/MSantibioticscritically ill patientstherapeutic drug monitoring
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