Universidade de Caxias do Sul (UCS), Instituto de Biotecnologia, Rua Francisco Getúlio Vargas, 1130 CEP 95070-560, Caxias do Sul, RS, Brazil; Universidade Federal do Rio Grande do Sul (UFRGS), Faculdade de Farmácia, Av. Ipiranga, 2752, CEP: 90610-000, Porto Alegre, RS, Brazil.
Universidade de Caxias do Sul (UCS), Instituto de Biotecnologia, Rua Francisco Getúlio Vargas, 1130 CEP 95070-560, Caxias do Sul, RS, Brazil.
J Pharm Biomed Anal. 2019 Sep 10;174:104-114. doi: 10.1016/j.jpba.2019.05.060. Epub 2019 May 27.
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 CHO 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.
乳酸盐和其盐的生物生产可以通过酶复合物葡萄糖-果糖氧化还原酶（GFOR）和运动发酵单胞菌的葡萄糖酸-δ-内酯酶（GL）来进行。考虑到这些化合物在制药领域的适用性，本研究的目的是评估乳酸钠、乳酸钾、乳酸钙和乳酸的加速和长期稳定性研究。此外，还进行了应激试验以评估对 pH 值、温度和氧化的稳定性。提交给降解试验的样品通过高效液相色谱法（HPLC）和高分辨率质谱分析（HRMS-ESI-QTOF）进行分析。考虑到加速（40°C 和 75%RH）和长期（30°C 和 75%RH）稳定性研究，乳酸盐和钙盐在六个月的分析中是稳定的。对于生物合成和市售的乳酸样品，都观察到了乳酸-δ-内酯的存在和水分的显著增加。在强制降解试验中，所有的乳酸盐和乳酸都表现出在碱性和酸性 pH 值条件下稳定，在 60 和 80°C 下稳定，并且也能抵抗紫外线照射。此外，还观察到了乳酸酸形式的存在。然而，在过氧化氢的存在下，乳酸和乳酸盐的降解是明显的。这种降解动力学曲线表明，乳酸盐遵循零级反应模型，而乳酸遵循二级动力学。主要降解产物的 MS 分析表明，一个分子公式 CHO 是由氧化脱羧产生的。本报告提供了大量的结果，作为对关于乳酸钠、乳酸钾、乳酸钙和乳酸的化学和物理化学稳定性的信息缺乏的补充。鉴于所引用化合物的多种用途，这些数据可能是有用的，并可作为参考。
