title: Intelligent peak deconvolution through in-depth study of the data matrix from liquid chromatography coupled with a photo-diode array detector applied to pharmaceutical analysis.
abstract: Multivariate curve resolution-alternating least squares (MCR-ALS) method was investigated for its potential to accelerate pharmaceutical research and development. The fast and efficient separation of complex mixtures consisting of multiple components, including impurities as well as major drug substances, remains a challenging application for liquid chromatography in the field of pharmaceutical analysis. In this paper we suggest an integrated analysis algorithm functioning on a matrix of data generated from HPLC coupled with photo-diode array detector (HPLC-PDA) and consisting of the mathematical program for the developed multivariate curve resolution method using an expectation maximization (EM) algorithm with a bidirectional exponentially modified Gaussian (BEMG) model function as a constraint for chromatograms and numerous PDA spectra aligned with time axis. The algorithm provided less than ±1.0% error between true and separated peak area values at resolution (Rs) of 0.6 using simulation data for a three-component mixture with an elution order of a/b/c with similarity (a/b)=0.8410, (b/c)=0.9123 and (a/c)=0.9809 of spectra at peak apex. This software concept provides fast and robust separation analysis even when method development efforts fail to achieve complete separation of the target peaks. Additionally, this approach is potentially applicable to peak deconvolution, allowing quantitative analysis of co-eluted compounds having exactly the same molecular weight. This is complementary to the use of LC-MS to perform quantitative analysis on co-eluted compounds using selected ions to differentiate the proportion of response attributable to each compound.
authors.affiliation: Eisai Co., Ltd., Formulation Research, Pharmaceutical Science & Technology Core Function Unit, Medicine Development Center, Kawashima, Kakamigahara, Gifu 501-6195, Japan.
authors.forename: Shuntaro
authors.initials: S
authors.lastname: Arase
authors.affiliation: Eisai Co., Ltd., Translational Medicine Department, Medicine Creation, Neurology Business Group, Tokodai, Tsukuba, Ibaraki 300-2635, Japan. Electronic address: k2-horie@hhc.eisai.co.jp.
authors.forename: Kanta
authors.initials: K
authors.lastname: Horie
authors.affiliation: Eisai Co., Ltd., Formulation Research, Pharmaceutical Science & Technology Core Function Unit, Medicine Development Center, Kawashima, Kakamigahara, Gifu 501-6195, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kato
authors.affiliation: Shimadzu Corporation, Technology Research Laboratory, Hikaridai, Seika-cho, Soraku-gun, Kyoto 619-0237, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Noda
authors.affiliation: Shimadzu Corporation, Research & Development Department, Analytical & Measuring Instruments Division, Nishinokyo Kuwabara-cho, Nakagyo-ku, Kyoto 604-8511, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Mito
authors.affiliation: Shimadzu Corporation, Research & Development Department, Analytical & Measuring Instruments Division, Nishinokyo Kuwabara-cho, Nakagyo-ku, Kyoto 604-8511, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Takahashi
authors.affiliation: Shimadzu Corporation, Research & Development Department, Analytical & Measuring Instruments Division, Nishinokyo Kuwabara-cho, Nakagyo-ku, Kyoto 604-8511, Japan. Electronic address: yanagisa@shimadzu.co.jp.
authors.forename: Toshinobu
authors.initials: T
authors.lastname: Yanagisawa
mesh_terms: D000098:Acetophenones / Q000032:analysis; D001577:Benzophenones / Q000032:analysis; D002073:Butanes / Q000032:analysis; D002851:Chromatography, High Pressure Liquid / Q000295:instrumentation / Q000379:methods; D003562:Cytidine / Q000032:analysis; D005464:Fluorobenzenes / Q000032:analysis; D007536:Isomerism; D007659:Ketones / Q000032:analysis; D016018:Least-Squares Analysis; D013058:Mass Spectrometry; D008970:Molecular Weight; D015999:Multivariate Analysis; D004364:Pharmaceutical Preparations / Q000032:analysis*; D011685:Purine Nucleotides / Q000032:analysis; D014498:Uracil / Q000032:analysis
chemical_list: D000098:Acetophenones; D001577:Benzophenones; D002073:Butanes; D005464:Fluorobenzenes; D007659:Ketones; D004364:Pharmaceutical Preparations; D011685:Purine Nucleotides; D014498:Uracil; D003562:Cytidine; C078616:4,4'-difluorobenzophenone; C547345:valerophenone
keywords: Chemometrics; Constraints; High-performance liquid chromatography (HPLC); MCR-ALS; Peak deconvolution; Photo diode array detector (PDA)