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Article

Determination of d-Cycloserine Impurities in Pharmaceutical Dosage Forms: Comparison of the International Pharmacopoeia HPLC–UV Method and the DOSY NMR Method

by 1,†, 2,3,†,‡, 4, 1,2,5 and 3,6,*
1
Slovenian NMR Centre, National Institute of Chemistry, Hajdrihova 19, SI-1000 Ljubljana, Slovenia
2
Faculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, SI-1001 Ljubljana, Slovenia
3
Lek Pharmaceuticals d.d., Sandoz Development Center Slovenia, Verovškova ulica 57, SI-1526 Ljubljana, Slovenia
4
Department of Food Chemistry, National Institute of Chemistry, Hajdrihova 19, SI-1000 Ljubljana, Slovenia
5
EN-FIST Centre of Excellence, Trg Osvobodilne fronte 13, SI-1000 Ljubljana, Slovenia
6
University of Ljubljana, Faculty of Pharmacy, Aškerčeva cesta 7, SI-1000 Ljubljana, Slovenia
*
Author to whom correspondence should be addressed.
These authors contributed equally.
Current position at: Biotechnology Development Unit, International Institute for Genetic Engineering and Biotechnology, Trieste, Italy
Molecules 2020, 25(7), 1684; https://doi.org/10.3390/molecules25071684
Received: 21 March 2020 / Revised: 1 April 2020 / Accepted: 3 April 2020 / Published: 7 April 2020
(This article belongs to the Special Issue Drug Analysis in Pharmaceutical Development and Drug Manufacturing)
d-cycloserine is a broad-spectrum antibiotic that is currently being used as a secondary choice in the treatment of tuberculosis. In recent years, it has become more popular, due to its effect on the nervous system. In this current study, we provide evidence that The International Pharmacopoeia HPLC–UV method for d-cycloserine impurity profiling is not repeatable due to the variable response of cycloserine dimer, one of d-cycloserine impurities. Therefore, we introduced the DOSY (diffusion ordered spectroscopy) NMR (nuclear magnetic resonance) technique to determine the levels of d-cycloserine impurities in pharmaceutical dosage forms. The DOSY NMR technique allowed separation of d-cycloserine, its degradation products, and key process impurities in concentrations below pharmacopoeial specification limits. The proposed DOSY NMR method allowed accurate identification and quantification of the cycloserine dimer, which was not possible through the use of the pharmacopoeial HPLC method. The current method has the potential for practical use in analytical laboratories of the pharmaceutical industry. View Full-Text
Keywords: d-cycloserine; cycloserine dimer; HPLC; NMR; DOSY d-cycloserine; cycloserine dimer; HPLC; NMR; DOSY
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MDPI and ACS Style

Makuc, D.; Švab, Ž.; Naumoska, K.; Plavec, J.; Časar, Z. Determination of d-Cycloserine Impurities in Pharmaceutical Dosage Forms: Comparison of the International Pharmacopoeia HPLC–UV Method and the DOSY NMR Method. Molecules 2020, 25, 1684. https://doi.org/10.3390/molecules25071684

AMA Style

Makuc D, Švab Ž, Naumoska K, Plavec J, Časar Z. Determination of d-Cycloserine Impurities in Pharmaceutical Dosage Forms: Comparison of the International Pharmacopoeia HPLC–UV Method and the DOSY NMR Method. Molecules. 2020; 25(7):1684. https://doi.org/10.3390/molecules25071684

Chicago/Turabian Style

Makuc, Damjan, Živa Švab, Katerina Naumoska, Janez Plavec, and Zdenko Časar. 2020. "Determination of d-Cycloserine Impurities in Pharmaceutical Dosage Forms: Comparison of the International Pharmacopoeia HPLC–UV Method and the DOSY NMR Method" Molecules 25, no. 7: 1684. https://doi.org/10.3390/molecules25071684

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