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AIM: To investigate the changes of bile acid metabolism in healthy adults after taking acetaminophen. METHODS: Ten healthy subjects were enrolled and the serum samples of subjects before and after multiple administration of acetaminophen were collected. They were divided into pre-dose group (PD), fifth-dose gro-up (FD) and eighth-dose group (ED). A high performance liquid chromatography-tandem mass spectrometric method (HPLC-MS/MS) was used to quantify 15 target-edbile acid metabolites in human plasma, combined with principal component analysis (PCA), orthogonal partial least squares discriminant analysis (OPLS-DA)to investigate the changes of bile acid metabolism profile in healthy adults after taking acetaminophen. And the biochemical indicators of each group were detected. RESULTS: There was a change in the bile acid spectrum of human serum after taking acetaminophen. Compared with group PD, the taurochenodeoxycholicacid (TCDCA), glycocholicacid (GCA), glycochenodeoxycholic acid (GCDCA) and tauroursodeoxycholic acid (TUDCA) levels were significantly increased (P<0.05). There was no obvious changes in biochemical indicators. GCA and GCDCA were the most sen-sitive indicators of bile acid. CONCLUSION: GCA and GCDCA can be used as potential biomarkers of early liver injury caused by acetaminophen.
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Objective The pathogenesis of intractable epilepsy was explored by examining the expression of the P-gp , GST-Pi as well as MDR1 in peripheral blood of the patients with intractable epilepsy. The potential of the above mentioned three genes as the biomarkers for treatment of intractable epilepsy was investigated. Methods Thirty-one sub?jects with refractory epilepsy, 33 subjects under good circumstances by antiepileptic drugs, and 37 healthy subjects were included in the present study. fluorescence quantitative polymerase chain reaction and flow cytometry were used to detect mRNA levels of MDR1 and GST-Pi and P-gp of MDR1 in the peripheral blood of the patients, respectively. Results The expression levels of MDR1 and GST-Pi were significantly higher in the AEDs intractable group(1.36±0.14,0.585±0.257) than in the treatment group(0.82±0.15,0.309±0.217, P<0.05)The expression levels of MDR1 and GST-Pi were signifi?cantly higher in the AEDs treatment group than in the normal group(0.27±0.07,0.134±0.223,P<0.05). The expression levels of P-gp were significantly higher in the AEDs of the intractable group(0.104±0.084)than in the treatment group (0.063 ± 0.030, P<0.05). The GST-Pi gene expression levels were significantly higher in three(0.535 ± 0.256)or two (0.425±0.254)kinds of antiepileptic drugs combination therapy than in single drug treatment(0.267±0.265, P<0.05). Leucocyte P-gp levels were significantly higher in combination therapy of three kinds of antiepileptic drugs(0.141 ± 0.096)than in combination therapy of two kinds of antiepileptic drugs(0.071±0.020)or in monotherapy(0.050±0.020, P<0.05). Conclusion MDR1 and GST-Pi gene expression levels of peripheral blood can be used as the reference in?dex for treatment of intractable epilepsy and the resistant index of combination treatment for intractable epilepsy.
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Objective To establish an LC-MS/MS method for the detection of landiolol concentration in human blood.Methods After pretreatment with neostigmine and a deproteinization procedure, landiolol and the internal standard venlafaxine were eluted isocratically using a mobile phase consisting of acetonitrile and 10 mmoL·L-1 ammonium acetate with 0. 1% formic acid in a ratio of 3664 ( V/V ) . Separation of the respective compounds was achieved on a Waters XTerra? RP18 column (150 mmí4. 6 mm,5 μm). Quantitative analysis of landiolol was conducted by a triple-quadrupole mass spectrometer with positive-electrospray ionization source,monitored under a multiple reaction monitoring ( MRM) mode. The extracted ions monitored following MRM transitions were m/z 510. 5→423. 1 for landiolol and m/z 278. 2→215. 1 for the internal standard venlafaxine. ResultsThe calibration curve of landiolol in human blood showed good linear relationship in the range of 1. 010-2 020 μg·L-1 . The lower limit of quantitation was 1. 010 μg · L-1 . The RSD of within-day and between-day precision was less than 6. 5% and 4. 8%, respectively. The recovery rate was 92. 6%-100. 9%. Conclusion The method is proven to be simple,rapid and reliable,and can be applied to study the pharmacokinetics of landiolol hydrochloride in healthy Chinese volunteers.