ABSTRACT
OBJECTIVE:To establish a method for the concentration determination of gabapentin (GBP) in human plasma.METHODS:After precipitated by methanol,using sulfamethoxazole as intemal standard,LC-MS/MS method was adopted.The determination was performed on Diamonsil C18 column with mobile phase consisted of water (containing 0.05％ formic acid)-methanol using a gradient elution program at the flow rate of 1 mL/min.The column temperature was 30 ℃,and sample size was 20 μL.The ESI was equipped and quantitative analysis was operated in positive ion and MRM mode.The mass transition ion-pairs were followed as m/z 172.0→154.1(GBP) and m/z 279.0→124.0 (internal standard).RESULTS:The linear range of GBP was 13.4-10 720.4 ng/mL (r=0.992 3,n=5).The limit of quantitation was 13.4 ng/mL,and the minimum detection limit was 4.0 ng/mL.RSDs of inter-day and intra-day were all lower than 10％.Relative errors ranged-4.93％-5.10％.The recoveries ranged 86.2％-90.3％ (RSD＜5％,n=6),and matrix effects ranged 87.6％-92.1％.The plasma concentration of GBP in 10 epileptic patients ranged 2 075.19-4 078.87 ng/mL (n=20).CONCLUSIONS:The method is proved to be sensitive,specific,practical and suitable for plasma concentration monitoring and pharmacokinetic study of GBP in epileptic patients.
ABSTRACT
OBJECTIVE:To investigate the effects of UGT1A6 and UGT1A9 gene polymorphisms on blood concentration of valproic acid in Han epileptic patients.METHODS:Totally 107 Chinese Han epileptic patients were selected from outpatient department of our hospital during Jan.2014-Apr.2015.They were given valproic acid monotherapy treatment for 3 months to 6 years.The steady state concentration ofvalproic acid was detected by EMIT.UGT1A6 (rs2070959,rs6759892) and UGT1A9 (rs13418420,rs2741045,rs2741049,rs6731242,rs72551330) genotypes were detected by MALDI-TOF-MS.The correlation of gene polymorphism with con centration dose ratios (CDR) of valproic acid was investigated.RESULTS:UGT1A9 rs72551330 mutation had not been detected,and the frequency of genotypes in other 6 sites were all in line with Hardy-Weinberg balance (P＞0.05).The CDR of valproic acid in pa tients with UGT1A6 rs2070959,rs6759892 mutation (AG+GG or TG+GG type) were significantly lower than those with wild homozy gote (AA or TT type),with statistical significance (P＜ 0.05).There was no statistical significance in CDR of valproic acid among patients with UGT1A9 rs13418420,rs2741045,rs2741049 and rs6731242 wild homozygote and mutation (P＞0.05).CONCLUSIONS:UGT1A6 rs2070959,rs6759892 gene polymorphisms of Han epileptic patients are associated with blood concentration of valproic acid,and the patients with UGT1A6 rs2070959,rs6759892 mutation need more dose ofvalproic acid.