TY  - JOUR
A1  - Monakhova, Yulia
A1  - Diehl, Bernd W.K.
T1  - Multinuclear NMR screening of pharmaceuticals using standardization by 2H integral of a deuterated solvent
JF  - Journal of Pharmaceutical and Biomedical Analysis
N2  - NMR standardization approach that uses the 2H integral of deuterated solvent for quantitative multinuclear analysis of pharmaceuticals is described. As a proof of principle, the existing NMR procedure for the analysis of heparin products according to US Pharmacopeia monograph is extended to the determination of Na+ and Cl- content in this matrix. Quantification is performed based on the ratio of a 23Na (35Cl) NMR integral and 2H NMR signal of deuterated solvent, D2O, acquired using the specific spectrometer hardware. As an alternative, the possibility of 133Cs standardization using the addition of Cs2CO3 stock solution is shown. Validation characteristics (linearity, repeatability, sensitivity) are evaluated. A holistic NMR profiling of heparin products can now also be used for the quantitative determination of inorganic compounds in a single analytical run using a single sample. In general, the new standardization methodology provides an appealing alternative for the NMR screening of inorganic and organic components in pharmaceutical products.
KW  - NMR spectroscopy
KW  - Inorganic ions
KW  - Heparin
KW  - Standardization
Y1  - 2022
SN  - 0731-7085
U6  - http://dx.doi.org/10.1016/j.jpba.2021.114530
VL  - 209
IS  - Article number: 114530
PB  - Elsevier
ER  - 
TY  - JOUR
A1  - Monakhova, Yulia
A1  - Diehl, Bernd W.K.
T1  - Nuclear magnetic resonance spectroscopy as an elegant tool for a complete quality control of crude heparin material
JF  - Journal of Pharmaceutical and Biomedical Analysis
N2  - Nuclear magnetic resonance (NMR) spectrometric methods for the quantitative analysis of pure heparin in crude heparin is proposed. For quantification, a two-step routine was developed using a USP heparin reference sample for calibration and benzoic acid as an internal standard. The method was successfully validated for its accuracy, reproducibility, and precision. The methodology was used to analyze 20 authentic porcine heparinoid samples having heparin content between 4.25 w/w % and 64.4 w/w %. The characterization of crude heparin products was further extended to a simultaneous analysis of these common ions: sodium, calcium, acetate and chloride. A significant, linear dependence was found between anticoagulant activity and assayed heparin content for thirteen heparinoids samples, for which reference data were available. A Diffused-ordered NMR experiment (DOSY) can be used for qualitative analysis of specific glycosaminoglycans (GAGs) in heparinoid matrices and, potentially, for quantitative prediction of molecular weight of GAGs. NMR spectrometry therefore represents a unique analytical method suitable for the simultaneous quantitative control of organic and inorganic composition of crude heparin samples (especially heparin content) as well as an estimation of other physical and quality parameters (molecular weight, animal origin and activity).
KW  - NMR spectroscopy
KW  - Heparin
KW  - Crude heparin
KW  - USP
KW  - Ions
Y1  - 2022
U6  - http://dx.doi.org/10.1016/j.jpba.2022.114915
SN  - 0731-7085
VL  - 219
IS  - Article number: 114915
PB  - Elsevier
CY  - New York, NY
ER  -