Title:Comparative Study of LC/MS and EMIT in Therapeutic Monitoring of Carbamazepine and its Clinical Applications
VOLUME: 13 ISSUE: 5
Author(s):Abdul Sami Shaikh, Fanlong Bu, Huanjun Liu, Chunmei Geng, Pingli Li, Meimei Gao, Rui Zhang* and Ruichen Guo*
Affiliation:Institute of Clinical Pharmacology, Qilu Hospital, Shandong University, Jinan, Institute of Clinical Pharmacology, Qilu Hospital, Shandong University, Jinan, Institute of Clinical Pharmacology, Qilu Hospital, Shandong University, Jinan, Institute of Clinical Pharmacology, Qilu Hospital, Shandong University, Jinan, Institute of Clinical Pharmacology, Qilu Hospital, Shandong University, Jinan, Institute of Clinical Pharmacology, Qilu Hospital, Shandong University, Jinan, Institute of Clinical Pharmacology, Qilu Hospital, Shandong University, Jinan, Institute of Clinical Pharmacology, Qilu Hospital, Shandong University, Jinan
Keywords:Antiepileptic drugs, carbamazepine, compare of LC/MS and EMIT, epilepsy, TDM, therapeutic monitoring.
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 (R
2= 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.
