Chemometric resolution of fully overlapped CE peaks: Quantitation of carbamazepine in human serum in the presence of several interferences

Abstract

Drug monitoring in serum samples was performed using second-order data generated by CE-DAD, processed with a suitable chemometric strategy. Carbamazepine could be accurately quantitated in the presence of its main metabolite (carbamazepine epoxide), other therapeutic drugs (lamotrigine, phenobarbital, phenytoin, phenylephrine, ibuprofen, acetaminophen, theophylline, caffeine, acetyl salicylic acid), and additional serum endogenous components. The analytical strategy consisted of the following steps: (i) serum sample clean-up to remove matrix interferences, (ii) data pre-processing, in order to reduce the background and to correct for electrophoretic time shifts, and (iii) resolution of fully overlapped CE peaks (corresponding to carbamazepine, its metabolite, lamotrigine and unexpected serum components) by the well-known multivariate curve resolution-alternating least squares algorithm, which extracts quantitative information that can be uniquely ascribed to the analyte of interest. The analyte concentration in serum samples ranged from 2.00 to 8.00 mg/L. Mean recoveries were 102.6% (s=7.7) for binary samples, and 94.8% (s=13.5) for spiked serum samples, while CV (%)=4.0 was computed for five replicate, indicative of the acceptable accuracy and precision of the proposed method.

Chemometric strategies for enhancing the chromatographic methodologies with second-order data analysis of compounds when peaks are overlapped

“…Matrixes N and M correspond to the determination of carbamazepine in the presence of interferences using capillary electrophoresis with DAD detector (see Ref. [54]). As can be seen in this figure, there is a difference of c.a.…”

“…Additional works involved the determination of dyes in beverages reaching a considerable reduction of the analysis time [12], and the resolution of fully overlapped capillary electrophoresis peaks applied to the quantitation of carbamazepine in human serum in the presence of several interferences [63]. It should be noticed that, owing to the complete overlapping among three of the analytes, the only algorithm capable of resolve this task was MCR-ALS.…”

“…In addition, Li and co-workers presented several strategies to enhance the quantitation of several analytes combining CE-DAD data and MCRALS [67][68][69]. Finally, we presented a challenging application in which three analytes, whose peaks were totally overlapped, could be determined in serum samples with acceptable analytical figures of merit [54].…”

Signal Processing Methods for Capillary Electrophoresis

“…However, a single model may be insufficient and the curve fitting process is complicated when there are overlapping peaks that are not baseline resolved (Dyson 1998). Usually in developing a CE method, the experimental conditions are optimised so as to ensure that all sample components are separated (Hanrahan et al 2008;Vera-Candioti et al 2008). However, such optimisation may not always be practicable and/or complete separation may be difficult, if not impossible, to achieve (Mammone et al 2007;Sentellas et al 2001;Zhang et al 2007).…”

“…An accurate peak model is required and, if the number of peaks is known, the model can then be fitted to the peaks that are overlapping using non-linear least squares curve fitting techniques. Such techniques have been applied to CE (Jarméus and Emmer 2008;Vera-Candioti et al 2008), as well as chromatography (Dasgupta 2008;Jin et al 2008;Vivó-Truyols et al 2005a, b), voltammetry (Huang et al 1995) and gel electrophoresis (Kitazoe et al 1983;Shadle et al 1997) to name but a few. Fig.…”