| Objective Establish a high performance liquid chromatography-mass spectrometry method for the rapid determination of lamotrigine concentration in patients with bipolar disorder after taking lamotrigine.To investigate the relationship between lamotrigine concentration and clinical efficacy,dosage and adverse reactions combined with the detection results.Methods Lamotrigine isotope was used as internal standard,and the plasma was achieved by protein precipitation using methanol.The analytes were performed using a Waters Cortecs C18 column(2.1×50mm,2.7μm)with 0.1% formic acid(v/v)aqueous solution and 0.1%formic acid(v/v)methanol solution as mobile phases at the flow rate of 0.4m L· min-1.The ion source was detected by positive electrospray ionization source(ESI+)and positive ion multiple reaction monitoring(MRM).Sixty patients diagnosed with bipolar II disorder admitted to our hospital between December 2021 and December 2022 were selected and treated with lamotrigine for 56 days.At baseline and at weeks 2,4,6 and 8 after treatment,the clinical efficacy and adverse reactions were assessed by Hamilton Depression Scale 24-item(HAMD-24),Hamilton Anxiety Scale(HAMA),Young’s Mania Scale(YMRS)and TESS.Plasma concentrations of lamotrigine at 2,4,6 and 8 weeks after treatment were determined by high performance liquid chromatography-mass spectrometry.The clinical efficacy was analyzed using the complete analysis set(FAS).SPSS 26.0 software was used to analyze the data.Bivariate correlation analysis was used to analyze the correlation between blood drug concentration and clinical efficacy,drug dosage and adverse reactions,and paired sample T-test was used to compare the efficacy before and after treatment.Receiver operating characteristic curve(ROC curve)was used to analyze whether lamotrigine plasma concentration predicted treatment effectiveness.Results The linear range of lamotrigine in plasma was 0.0989-19.78μg·m L-1.The Lowest detection limit is 0.10μg·m L-1.The relative standard deviations(RSDS)of both day and day were less than 3%,and the recoveries were up to 85%.After taking lamotrigine for bipolardisorder,HAMD scores and HAMA scores at the 2nd,4th,6th and 8th week of treatment were all lower than those before treatment(t = 26.92,22.55,P < 0.01)and those before treatment(t = 17.08,17.83,P < 0.01).There were no significant changes in YMRS scores(t =5.39,6.48,P > 0.05).There were statistically significant differences between the blood concentration and dosage of lamotrigine(r = 0.586,0.535,0.497,0.826,P < 0.01),but no statistically significant differences between the blood concentration and HAMD score(r =0.184,0.043,0.124,0.149,P > 0.05),there was no significant difference in the reduction rate of HAMD(r = 0.058,0.074,0.033,0.009,P > 0.05).ROC curve analysis showed that the area under the curve of lamotrigine concentration predicting treatment effectiveness was0.748(95% confidence interval: 0.669--0.827,P < 0.001),and the cut-off value(1.17)was Selected according to the maximum Yoden index(about 0.413),the sensitivity was 81.3%,and the specificity was 60%.Conclusion:The method is convenient,accurate and specific,has higher sensitivity and stronger selectivity,and is suitable for monitoring the blood concentration of lamotrigine in patients with bipolar disorder.The plasma concentration of lamotrigine was positively correlated with the dose,and was not significantly correlated with the reduction rate of HDMA,but it had certain value in predicting the effectiveness of treatment in patients.There was no significant difference between blood drug concentration and TESS score. |
