Simultaneous Determination Of Anti-HIV Drugs And Glucocorticoids In Hair With Liquid Chromatography-tandem Mass Spectrometry

Anti-HIV drugs are antiretroviral drugs which inhibit the replication of HIV.The assay method for detecting the concentration of anti-HIV drugs in hair can be used for the evaluation of long-term adherence to predict the long-term treatment outcomes of HIV patients.In current China,tenofovir,lamivudine and nevirapine are the important drugs in the first-line antiretroviral therapeutic regimens of National Free Antiretroviral Treatment Program.However,there was no study reporting simultaneous determination of the three drugs' concentration in hair.On the other hand,HIV patients often suffered from long-term psychological stress and negative emotional symptoms,such as anxiety and depression which resulted in drugs abuse and reducing treatment outcomes.Cortisol and cortisone in hair are important indexes for evaluating long-term psychological stress and negative emotional symptoms.The measurement of glucocorticoid can be used to monitor the mental health of patients.Therefore,this study firstly aimed to develop a novel and sensitive LC-MS/MS method for simultaneous determination of anti-HIV drugs and glucocorticoids in hair.Then the method was applied to evaluate the long-term adherence to the treatment and to investigate the related factors influencing the evaluation of long-term adherence.Finally,the method was used to examine the association of the concentration of anti-HIV drugs with glucocorticoids in the hair of HIV patients.The present analysis mthods for simultaneous determination of anti-HIV drugs and glucocorticoids were developed based on both 2-mg and 10-mg hair(Methods 1 and 2)under ESI in the positive mode and multiple reactions monitoring(MRM).Method 1 showed its limits of quantitation for tenofovir,lamivudine,nevirapine,cortisol and cortisone at 40,12,10,12 and 10 pg/mg.The inter-and intra-day coefficients of variation were less than 16.0 % and the recovery was ranged from 80.6 % to 122.3 %.Method 2 showed its limits of quantitation for tenofovir,lamivudine,nevirapine,cortisol and cortisone at 36,15,6,3 and 8 pg/mg.The inter-and intra-day coefficients of variation were within 15.0 % and the recovery was ranged from 83.1 % to 114.4 %.Method 2 showed high accuracy and reproducibility than Method 1.The population analysis with Method 2 revealed that the concentrations in hair were decreased with the distance of hair segment away from the scalp for the three drugs.There were also high inter-individual and inter-drug variations of the three drugs in hair.There was no significant association of the concentration of anti-HIV drugs with glucocorticoids in hair samples.