Study On The Influence Of Diet On The Behaviors In Pharmacokinetic Of Linezolid

PurposeLinezolid is developed for clinical treatment of severe gram positive bacteria infection as new oxazolidone antibiotics by Pharmacia Upjohn company,inhibition of bacteria of linezolid by inhibiting the formation of 70S,so as to achieve the antibacterial effect.Because of its unique antibacterial mechanism,it will not cross resistance with other antibiotics,and its oral bioavailability is almost 100%.Therefore,linezolid is widely used in clinical treatment.In this study,an accurate liquid chromatography-tandem mass spectrometry（LC-MS/MS）methed was developed for determination of fasting and postprandial state for oral concentration in healthy human plasma after administration of linezolid,and analyze and compare the pharmacokinetic parameters in the two kinds of states.MethodProtein precipitation was used to purified with methanol containing 0.2%formic acid,after appropriate dilution with the mobile phase isolated by chromatographic column which is Agilent ZORBAX 300SB C8（4.6×50 mm I.D,5μm）,1.0%formic acid methanol-1.0%formic acid-water as mobile phase,using gradient elution elution separation;using electrospray ion source（ESI）,detection mode of multiple reaction monitoring（MRM）under positive ion detection,the analysis time is 4.5 min;for the quantitative response of ion pairs were linezolid（m/z 338.1?296.2）;isotope internal standard（m/z 341.2?297.3）,according to the requirements of CFDA in precision and accuracy,matrix effect,hemolytic effect the stability and other aspects the complete method was validated.Using the LC-MS/MS analysis method of plasma samples of healthy volunteers in fasting and postprandial state taking linezolid for content analysis,the relevant pharmacokinetic parameters(including AUC_0-∞、t_1/2、T_max and C_max)were calculated and draw the plasma concentration time curve,and the above two kinds of different condition pharmacokinetic parameters were compared and analyzed.ResultsThe determination of the concentration of linezolid in human plasma by LC-M S/MS method established in this study is simple,accurate,and precision accura cy can meet the government and batch quantity analysis requirements,and end ogenous plasma impurities and hemolysis will not affect the results of this met hod,extraction recovery is better with this pretreatment method,stability study showed that linezolid in plasma separation,storage,transportation and during th e analysis the testing process has good stability,without special processing and preservation in the above process,the method can meet the requirements of t he standards of government and the testing requirements of high-throughput ana lysis,which can be used for clinical trial analysis.In healthy human blood con centration of linezolid during the fasting and postprandial state,respectively,AUC_0-t were 95.244±36.225μg/m L*h and 82.763±21.075μg/m L*h,AUC_0-∞were 104.797±34.143μg/mL*h and 91.99±23.058μg/mL*h,R_AUC_t/∞were 89.863±7.272%and 90.304±8.326%,Vd value were 32.290±11.125 L and 32.886±10.451 L,MRT_0-twere 4.967±0.896 h and 5.716±1.331 h,MRT_0-∞were 6.361±1.175 h an d 7.013±1.520 h,CL were 6.252±1.760 L/h and 6.922±1.708 L/h,C_max were 17.582±6.03 3mg/L and 13.552±2.925 mg/L,T_maxax were 1.177±1.165 min and 2.469±1.61 min,t_1/2 were 3.662±1.017 h and 3.45±1.197 h.The postprandial state h as statistically significant difference in C_max and T_max compared with the fasting state（p value<0.05）,and the peak concentration decreased,the peak time pr olonged and the absorption degree decreased after meal.