TY - JOUR

T1 - Improving reliability of chemometric models for authentication of species origin of heparin by switching from 1D to 2D NMR experiments

AU - Монахова, Юлия Борисовна

AU - Diehl, Bernd

AU - Fareed, Jaweed

AU - Yao, Yiming

N1 - Funding Information: Y. Monakhova acknowledges support of the Russian Ministry of Science and Education (project 4.1063.2017/4.6 ).

PY - 2018/5/10

Y1 - 2018/5/10

N2 - Nuclear magnetic resonance (NMR) spectroscopy is regarded as one of the most powerful and versatile analytical approaches to assure the quality of heparin preparations. In particular, it was recently demonstrated that by using 1H NMR coupled with chemometrics heparin and low molecular weight heparin (LMWH) samples derived from three major animal species (porcine, ovine and bovine) can be differentiated [Y.B. Monakhova et al. J. Pharm. Anal. 149 (2018) 114–119]. In this study, significant improvement of existing chemometric models was achieved by switching to 2D NMR experiments (heteronuclear multiple-quantum correlation (HMQC) and diffusion-ordered spectroscopy (DOSY)). Two representative data sets (sixty-nine heparin and twenty-two LMWH) belonged to different batches and distributed by different commercial companies were investigated. A trend for animal species differentiation was observed in the principal component analysis (PCA) score plot built based on the DOSY data. A superior model was constructed using HMQC experiments, where individual heparin (LMWH) clusters as well as their blends were clearly differentiated. The predictive power of different classification methods as well as unsupervised techniques (independent components analysis, ICA) clearly proved applicability of the model for routine heparin and LMWH analysis. The switch from 1D to 2D NMR techniques provides a wealth of additional information, which is beneficial for multivariate modeling of NMR spectroscopic data for heparin preparations.

AB - Nuclear magnetic resonance (NMR) spectroscopy is regarded as one of the most powerful and versatile analytical approaches to assure the quality of heparin preparations. In particular, it was recently demonstrated that by using 1H NMR coupled with chemometrics heparin and low molecular weight heparin (LMWH) samples derived from three major animal species (porcine, ovine and bovine) can be differentiated [Y.B. Monakhova et al. J. Pharm. Anal. 149 (2018) 114–119]. In this study, significant improvement of existing chemometric models was achieved by switching to 2D NMR experiments (heteronuclear multiple-quantum correlation (HMQC) and diffusion-ordered spectroscopy (DOSY)). Two representative data sets (sixty-nine heparin and twenty-two LMWH) belonged to different batches and distributed by different commercial companies were investigated. A trend for animal species differentiation was observed in the principal component analysis (PCA) score plot built based on the DOSY data. A superior model was constructed using HMQC experiments, where individual heparin (LMWH) clusters as well as their blends were clearly differentiated. The predictive power of different classification methods as well as unsupervised techniques (independent components analysis, ICA) clearly proved applicability of the model for routine heparin and LMWH analysis. The switch from 1D to 2D NMR techniques provides a wealth of additional information, which is beneficial for multivariate modeling of NMR spectroscopic data for heparin preparations.

KW - Animal origin

KW - Classification

KW - DOSY

KW - Heparin

KW - HMQC

KW - NMR spectroscopy

UR - http://www.scopus.com/inward/record.url?scp=85042514723&partnerID=8YFLogxK

U2 - 10.1016/j.jpba.2018.02.041

DO - 10.1016/j.jpba.2018.02.041

M3 - Article

VL - 153

SP - 168

EP - 174

JO - Journal of Pharmaceutical and Biomedical Analysis

JF - Journal of Pharmaceutical and Biomedical Analysis

SN - 0731-7085

ER -