An HPLC Method for Simultaneous Determination of Concentrations of Linezolid and its Metabolites PNU-142300 and PNU-142586 in Human Plasma
OBJECTIVE To establish a high-performance liquid chromatography method for simultaneous determination of linezolid and its main metabolites PNU-142300 and PNU-142586 in human plasma,and monitor the blood concentration of critically ill patients.METHODS The determination was performed on Diamonsil C18 column(4.6 mm ×250 mm,5 μm)with chloramphenicol as internal standard,acidified acetonitrile as protein precipitator,and bisolvent mobile phase consisting of A acetonitrile,B citric acid(0.1 mol·L-1)-sodium hydrogen phosphate(0.2 mol·L-1)buffer solution(pH 3.0).The flow rate was 0.5 mL·min-1,the detection wavelength was set at 254 nm,the column temperature was maintained at 30 ℃,and the sample size was 20 µL.RESULTS Linezolid had a good linear relationship in the concentration range of 0.5-40 µg·mL-1(r=0.999 9).The lower limit of quantitation was 0.5 μg·mL-1,and the detection limit was 0.1 μg·mL-1.PNU-142300 and PNU-142586 had good linear relationship in the concentration range of 0.5-20 μg·mL-1(r=0.999 8 and r=0.999 6),the lower limit of quantitation was 0.5 μg·mL-1,and the detection limit was 0.2 μg·mL-1.In 10 critically ill patients,plasma linezolid and PNU-142300 and PNU-142586 were 3.62,1.88 and 2.30 times higher in patients with renal insufficiency than in patients with normal renal function,respectively.There was a strong correlation between exposure of linezolid and its metabolites and thrombocytopenia and anemia.CONCLUSION The method is simple,sensitive,and accurate,and can be used to monitor the blood concentration of linezolid and its metabolites PNU-142300 and PNU-142586 in critically ill patients and study the correlation of adverse reactions.
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