Abstract
Lamotrigine (LTG) and oxcarbazepine (OXC) are first-line drugs for epilepsy treatment. Their large pharmacokinetics variabilities and relations between efficacy and toxicity and blood plasma concentration require routine monitoring for dose adjustment. In this study, we developed and validated a simple, accurate, and reliable method for simultaneous determination of LTG, OXC and 10,11-dihydro-10-hydroxycarbazepine (MHD) in human blood plasma by high-performance liquid chromatography-ultraviolet detection (HPLC-UV) with a simple one-step protein precipitation using methanol (1% acetic acid) and 15 min elution time under isocratic elution at 1 mL/min. Calibration range was 2.4 to 120 mg/L for LTG, OXC, and MHD. The intra-day and inter-day bias were − 8.84 to 4.18%, and the imprecision was less than 8.08% for all analytes. The internal standard (fluconazole) normalized recovery was 96.30 to 107.69% for LTG, 98.51 to 111.04% for MHD, and 95.04 to 109.86% for OXC. A total of 186 LTG samples and 25 MHD samples were used to evaluate the agreement between HPLC-UV and ultra-performance liquid chromatography-mass spectrometry (UHPLC-MS/MS) by Passing-Bablok regression and Bland-Altman plot. The mean bias and the 95% limits of agreement (95% LOA) of the two measurements were 0.575 mg/L and − 1.238 to 2.387 mg/L for LTG (n = 186) and − 1.222 mg/L and − 8.271 to 5.827 mg/L for MHD (n = 25), which indicated the UV method was comparable with the MS method for LTG and MHD analysis.
Highlights
Drug therapy is the most important treatment for epilepsy control for most of the patients (Palte et al, 2018)
During routine clinical application of the method, we found that an alternative method was required due to the following reasons: immunoassay for LTG, OXC, and MHD measurement is not available in China; for routine monitoring of clinical samples, the LC-MS should be ready during the work day, which resulted in big dissipate of machine-hour; UV method was more affordable for routine monitoring than the LC-MS method, especially in developing countries like China; and during the longtime clinical application, LC-MS might be shut down due to various troubles, the drug monitoring should not be interrupted to ensure medical quality
Selectivity and lower limit of quantitation (LLOQ) The selectivity was assessed by comparing the peak area of analytes- and Internal standard (IS)-free plasma from six individuals with those of LLOQ samples
Summary
Drug therapy is the most important treatment for epilepsy control for most of the patients (Palte et al, 2018). LTG is widely used in monotherapy and combined therapy for epilepsy control, especially for special populations such as children, the elderly, and pregnant women (Italiano & Perucca, 2013; Westley & Morris, 2008). LTG plasma level could be affected by various factors including age, pregnancy, liver and kidney function, smoking, genetic background, and combined medication (Italiano & Perucca, 2013; Petrenaite et al, 2005; Clark et al, 2013; Lovric et al, 2018; Brzakovic et al, 2012; Milosheska et al, 2016). LTG dose adjustment is a challenge for clinicians and pharmacist to achieve satisfied efficacy and avoid life-threatening toxicity
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