title: Qualitative and simultaneous quantitative analysis of cimetidine polymorphs by ultraviolet-visible and shortwave near-infrared diffuse reflectance spectroscopy and multivariate calibration models.
abstract: The object of the present study was to investigate the feasibility of applying ultraviolet-visible and shortwave near-infrared diffuse reflectance spectroscopy (UV-vis-SWNIR DRS) coupled with chemometrics in qualitative and simultaneous quantitative analysis of drug polymorphs, using cimetidine as a model drug. Three polymorphic forms (A, B and D) and a mixed crystal (M1) of cimetidine, obtained by preparation under different crystallization conditions, were characterized by microscopy, X-ray powder diffraction (XRPD) and infrared spectroscopy (IR). The discriminant models of four forms (A, B, D and M1) were established by discriminant partial least squares (PLS-DA) using different pretreated spectra. The R and RMSEP of samples in the prediction set by discriminant model with original spectra were 0.9959 and 0.1004. Among the quantitative models of binary mixtures (A and D) established by partial least squares (PLS) and least squares-support vector machine (LS-SVM) with different pretreated spectra, the LS-SVM models based on original and MSC spectra had better prediction effect with a R of 1.0000 and a RMSEP of 0.0134 for form A, and a R of 1.0000 and a RMSEP of 0.0024 for form D. For ternary mixtures, the established PLS quantitative models based on normalized spectra had relatively better prediction effect for forms A, B and D with R of 0.9901, 0.9820 and 0.9794 and RMSEP of 0.0471, 0.0529 and 0.0594, respectively. This research indicated that UV-vis-SWNIR DRS can be used as a simple, rapid, nondestructive qualitative and quantitative method for the analysis of drug polymorphs.
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu 610065, PR China.
authors.forename: Yuyan
authors.initials: Y
authors.lastname: Feng
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu 610065, PR China.
authors.forename: Xiangling
authors.initials: X
authors.lastname: Li
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu 610065, PR China.
authors.forename: Kailin
authors.initials: K
authors.lastname: Xu
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu 610065, PR China.
authors.forename: Huayu
authors.initials: H
authors.lastname: Zou
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu 610065, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu 610065, PR China. Electronic address: lianngbing@sina.com.
authors.forename: Bing
authors.initials: B
authors.lastname: Liang
mesh_terms: D002138:Calibration; D002927:Cimetidine / Q000032:analysis* / Q000737:chemistry; D003460:Crystallization / Q000379:methods; D056951:Photoelectron Spectroscopy / Q000379:methods; D019265:Spectroscopy, Near-Infrared / Q000379:methods; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D002927:Cimetidine
keywords: Cimetidine polymorphs; Least squares-support vector machine; Partial least squares; Ultraviolet–visible and shortwave near-infrared diffuse reflectance spectroscopy