@article{3219876,
    title = "Chemometrically Assisted Optimization of Pregabalin Fluorescent Derivatization Reaction with a Novel Xanthone Analogue and Validation of the Method for the Determination of Pregabalin in Bulk via a Plate Reader",
    author = "Kritikos, N. and Iliou, A. and Kalampaliki, A.D. and Gikas, E. and Kostakis, I.K. and Michel, B.Y. and Dotsikas, Y.",
    journal = "Molecules (Basel, Switzerland)",
    year = "2022",
    volume = "27",
    number = "6",
    publisher = "MDPI",
    doi = "10.3390/molecules27061954",
    keywords = "amine;  coloring agent;  dyes, reagents, indicators, markers and buffers;  pregabalin;  xanthone derivative, Amines;  Coloring Agents;  Indicators and Reagents;  Pregabalin;  Xanthones",
    abstract = "Quantitation of chromophore-free analytes is always a challenge. To this purpose, derivati-zation of the analyte constitutes a common strategy, leading to a product with a strong signal. In the current study, a novel xanthone analogue was utilized for the first time for the derivatization of pregabalin, a model analyte with a primary amine moiety that lacks a chromophore. The fact that only the xanthene-based derivative, formed after the derivatization reaction fluoresces, enables avoiding its chromatographic separation from the reagent and thus reducing the analysis time of a series of samples in 1–2 min via a plate reader. The reaction conditions were optimized via a central composite design (CCD), with fluorescence signal as the measure of the yield. The following factors that affect the derivatization reaction were chosen: (a) temperature, (b) reaction time, and (c) triethylamine solution volume used to drive the reaction to completion. After the identification of the optimal conditions, the method was validated according to ICH guidelines, using a fluorescence plate reader for signal measurement (λex = 540, λem = 615 nm). Finally, the newly developed high-throughput method was applied to the determination of drug content in pregabalin bulk. © 2022 by the authors. Licensee MDPI, Basel, Switzerland."
}