Abstract
Background: Carbamazepine (CBZ) has a narrow therapeutic index that urges therapeutic drug monitoring (TDM) to ensure its efficacy and prevent toxicity. Several accurate and sensitive chromatography methods are available for TDM of CBZ but are not used routinely due to expensive instrumentation, time consuming and complicated procedures. Enzyme-multiplied immunoassay technique (EMIT) is used in routine TDM of CBZ due to simple, rapid and easy use. The aim of this study is to evaluate the correlation between Liquid chromatography-mass spectrometry (LC/MS) assay and routinely used EMIT assay for TDM of CBZ concentration in human plasma and to offer a guide for clinical and pathological laboratories in clinical settings.
Methods: The blood samples of 103 epileptic patients using CBZ were collected for TDM. The TDM was performed by two different types of assay methods i.e. LC/MS and EMIT. The correlation between two different assays was evaluated in 93 patients with statistical analysis of Bland-Altman plot and deming regression analysis in MedCalc software and statistical package for the social sciences (SPSS), respectively. Results: The TDM results of CBZ obtained by LC/MS and EMIT assays were evaluated for correlation in 93 epileptic patients because the results of 10 patients were below the lower limit of quantification (LLOQ) of EMIT. The correlation between two methods was good (R2= 0.971) but carbamazepine plasma concentrations determined by EMIT were slightly higher than LC/MS. The 95% confidence interval was 0.94~2.74 µg/mL. The coefficient of variation (CV) of intra and inter-day were below 3% in LC/MS method. The calibration curves exhibited decent linearity in the 5.0-1000 ng/mL concentration range for LC/MS and 2-20 µg/mL for EMIT. The LLOQ of LC/MS and EMIT was 5 ng/mL and 2 µg/mL, respectively, which suggested that LLOQ of LC/MS is 400 times lower than EMIT. Conclusion: The correlation between results of LC/MS and EMIT assays for TDM of CBZ in 93 epileptic patients was evaluated. There was a slight difference between these two methods with EMIT providing slightly higher concentration levels of CBZ than concentrations levels provided by LC/MS, but further evaluation is needed. The results of LC/MS method are more precise and acceptable. However, a good correlation still exists between the two methods. EMIT is faster, cheaper and requires less time and can be used as alternative choice in TDM of CBZ.Keywords: Antiepileptic drugs, carbamazepine, compare of LC/MS and EMIT, epilepsy, TDM, therapeutic monitoring.
Graphical Abstract
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