Abstract
AbstractHeat stress studies have been conducted in support of developing a heat-stable liquid solution of dalbavancin. The degradation products that form in heat-stressed buffered dalbavancin solutions have been identified, including the known major degradation product, mannosyl aglycone (MAG), and four previously uncharacterized compounds. Liquid chromatography-mass spectrometry/mass spectrometry (LC–MS/MS) was used to identify the degradation products of dalbavancin in acetate- and phosphate-buffered solutions under thermal stress at 70 °C and the changes in the degradation pattern in the presence of 2HPβCD and divalent metal ions. Although Ca2+, Mg2+, and Zn2+ did not reduce dalbavancin degradation under thermal stress in acetate buffer, 2HPβCD significantly reduced its overall degradation, in particular, the formation of MAG. This protective effect was enhanced by the addition of Ca2+ to the formulation. In phosphate buffer, MAG formation was also reduced by the addition of 2HPβCD, although significant increases in other degradation products were observed in this case. The addition of Mg2+ to 2HPβCD significantly reduced the overall degradation while increasing MAG formation somewhat. The results strongly suggest that 2HPβCD forms a complex with the hydrophobic glycone tail of dalbavancin, suppressing hydrolysis of the glycosidic bond.
Publisher
Springer Science and Business Media LLC
Reference24 articles.
1. Al Toma RS, Brieke C, Cryle MJ, Süssmuth RD (2015) Structural aspects of phenylglycines, their biosynthesis and occurrence in peptide natural products. Nat Prod Rep 32:1207-1235
2. Alebic-Kolbah T, Demers R, Cojocaru L (2011) Dalbavancin: quantification in human plasma and urine by a new improved high performance liquid chromatography–tandem mass spectrometry method. J Chromatogr B Analyt Technol Biomed Life Sci 879(25):2632-2641
3. Avataneo V, Antonucci M, De Vivo ED, Briozzo A, Cusato J, F. Bermond F et al (2021) Validation and clinical application of a new liquid chromatography coupled to mass spectrometry (HPLC-MS) method for dalbavancin quantification in human plasma. Separations 8:189
4. Bazin H, Bouchu A, Descotes G, Petit-Ramel M (1995) Comparison of calcium complexation of some carboxylic acids derived from D-glucose and D-fructose. Can J Chem 73:1338–1347
5. Belissa E, Nino C, Bernard M, Henriet T, Sadou-Yaye H, Surget E et al (2014) Liquid chromatography–tandem mass spectrometry for simultaneous determination of ticarcillin and vancomycin in presence of degradation products. Application to the chemical stability monitoring of ticarcillin-vancomycin solutions. J Chromatogr Sep Tech. 5:5
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