Sodium, potassium, calcium lactobionates, and lactobionic acid from Zymomonas mobilis: A novel approach about stability and stress tests

J Pharm Biomed Anal. 2019 Sep 10:174:104-114. doi: 10.1016/j.jpba.2019.05.060. Epub 2019 May 27.

Abstract

The bioproduction of lactobionic acid and its salts can be performed by enzymatic complex glucose-fructose oxidoreductase (GFOR) and glucono-δ-lactonase (GL) of Zymomonas mobilis. Considering the applicability of these compounds in pharmaceutical area, the aim of this study was to assess the accelerated and long-term stability studies of sodium, potassium, calcium lactobionate, and lactobionic acid. Furthermore, stress tests were performed to evaluate the stability against pH, temperature and oxidation. The samples submitted to degradation tests were analyzed by high-performance liquid chromatography (HPLC) and high-resolution mass spectrometry analysis (HRMS-ESI-QTOF). Sodium, potassium, and calcium lactobionate were stable for six months of analyses considering the accelerated (40 °C and 75% RH) and long-term (30 °C and 75% RH) stability studies. The presence of lactobiono-δ-lactone and a significant increase in moisture were observed for both biosynthesized and commercially available lactobionic acid samples. Against the forced degradation tests, all the lactobionate salts and lactobionic acid showed to be stable upon alkaline and acid pH conditions, at 60 and 80 °C, and also against UV light exposition. Furthermore, the presence of lactobiono-δ-lactone form was observed in lactobionic acid samples. However, the degradation of both lactobionic acid and lactobionate salts was evident in the presence of hydrogen peroxide. This degradation kinetic profile suggests, that lactobionate salts follows a zero-order reaction model and lactobionic acid follows a second-order kinetic. The MS analysis of the main degradation product suggests a molecular formula C11H20O10 resulting from the oxidative decarboxylation. This report brings an amount of results as contribution to the scarce information regarding the chemical and physical-chemical stability of sodium, potassium, calcium lactobionate, and lactobionic acid. These data may be useful and serve as reference, in view of the multipurpose applications of the cited compounds.

Keywords: Lactobionate salts; Lactobionic acid; Oxidative degradation; Stability study; Stress tests; Zymomonas mobilis.

MeSH terms

  • Bioreactors
  • Calcium / chemistry*
  • Decarboxylation
  • Disaccharides / chemistry*
  • Drug Stability
  • Hydrogen Peroxide / chemistry
  • Hydrogen-Ion Concentration
  • Kinetics
  • Lactones
  • Mass Spectrometry
  • Oxidative Stress
  • Oxidoreductases / chemistry
  • Oxygen / chemistry
  • Potassium / chemistry*
  • Sodium / chemistry*
  • Temperature
  • Ultraviolet Rays
  • Zymomonas / chemistry*

Substances

  • Disaccharides
  • Lactones
  • lactobionic acid
  • Sodium
  • Hydrogen Peroxide
  • Oxidoreductases
  • glucose-fructose oxidoreductase
  • Potassium
  • Oxygen
  • Calcium