TY - JOUR

T1 - Nuclear magnetic resonance spectroscopy as a tool for thequantitative analysis of water and ions in pharmaceuticals: Exampleof heparin

AU - Монахова, Юлия Борисовна

AU - Diehl, Bernd

N1 - Funding Information: We warmly thank K. Seitz and T. Lüke for their excellent technical assistance. We thank Professor Fareed and Dr. Yao for providing samples of ovine origin. Y. Monakhova acknowledges support of the Russian Ministry of Science and Education (project 4.1063.2017/4.6). Appendix A

PY - 2018/5/30

Y1 - 2018/5/30

N2 - Heparin is a linear, highly sulfated glycosaminoglycan (GAG), which consists of repeating disaccharide units of β-D-glucuronic acid or α-L-iduronic acid and α-D-glucosamine. While robust analytical approaches exist for the characterization of organic composition of heparin preparations, there is a lack of methods for the simultaneous quantification of inorganic compounds (water, anions, cations) in this matrix. A nuclear magnetic resonance (NMR) spectrometric method for heparin characterization described in US Pharmacopeia was extended to simultaneous analysis of the inorganic ions (sodium, calcium, and chloride), acetate as well as water content. NMR control of these parameters is possible with only one sample preparation according to the US Pharmacopeia using just four sequential NMR experiments ( 1H, 2D, 23Na, and 35Cl) with a total measurement time less than 20 min. Validation results in terms of precision, reproducibility, limit of detection and recovery demonstrated that the developed method is fit-for-purpose for the authentic heparin samples. The quantitative data for a representative set of more than hundred Na- and Ca- heparin and low-molecular weight heparin (LMWH) samples were discussed regarding animal origin and the type of anticoagulant. NMR spectrometry represents a unique analytical method suitable for the simultaneous quantitative control of organic and inorganic composition of heparin.

AB - Heparin is a linear, highly sulfated glycosaminoglycan (GAG), which consists of repeating disaccharide units of β-D-glucuronic acid or α-L-iduronic acid and α-D-glucosamine. While robust analytical approaches exist for the characterization of organic composition of heparin preparations, there is a lack of methods for the simultaneous quantification of inorganic compounds (water, anions, cations) in this matrix. A nuclear magnetic resonance (NMR) spectrometric method for heparin characterization described in US Pharmacopeia was extended to simultaneous analysis of the inorganic ions (sodium, calcium, and chloride), acetate as well as water content. NMR control of these parameters is possible with only one sample preparation according to the US Pharmacopeia using just four sequential NMR experiments ( 1H, 2D, 23Na, and 35Cl) with a total measurement time less than 20 min. Validation results in terms of precision, reproducibility, limit of detection and recovery demonstrated that the developed method is fit-for-purpose for the authentic heparin samples. The quantitative data for a representative set of more than hundred Na- and Ca- heparin and low-molecular weight heparin (LMWH) samples were discussed regarding animal origin and the type of anticoagulant. NMR spectrometry represents a unique analytical method suitable for the simultaneous quantitative control of organic and inorganic composition of heparin.

KW - Heparin

KW - Inorganic ions

KW - NMR spectroscopy

KW - Water content

UR - http://www.scopus.com/inward/record.url?scp=85044101836&partnerID=8YFLogxK

U2 - 10.1016/j.jpba.2018.03.028

DO - 10.1016/j.jpba.2018.03.028

M3 - Article

VL - 154

SP - 332

EP - 338

JO - Journal of Pharmaceutical and Biomedical Analysis

JF - Journal of Pharmaceutical and Biomedical Analysis

SN - 0731-7085

ER -