Abstract

The antimicrobial chlorhexidine is considered the gold standard in dentistry. Thymol is a phenol found in the essential oils of various plant species and also stands out for its antimicrobial potential. Synergistic effects can be promoted by applying these two active pharmaceutical ingredients together in technological products, for example in controlled release microparticles. The objective of this work was to develop and validate an analytical methodology applying a Box-Behnken experimental design and using High Performance Liquid Chromatography capable of quantifying chlorhexidine and thymol simultaneously in a matrix including pharmaceutical excipients. After optimization, the mobile phase consisted of methanol and 0.03 M monobasic sodium phosphate buffer (60:40), with 0.4% triethylamine and octylsilane as the applied stationary phase. The method proved selective, even in the presence of chlorhexidine and thymol degradation products. For chlorhexidine, the method was linear from 4.8 to 19.2 µg/mL, and for thymol from 8.0 to 32.0 µg/mL. Accuracy was close to 100%, and the precision assessment yielded coefficient variation values of <5%. Being based on the Box-Behnken design, the method was robust and therefore validated for assisting in quality control processes involving these active pharmaceutical ingredients.

摘要

抗菌氯己定被认为是牙科的金标准。百里酚是一种存在于多种植物精油中的苯酚，还因其抗菌潜力而引人注目。通过将这两种活性药物成分一起应用于技术产品（例如控释微粒）中，可以促进协同效应。这项工作的目的是开发和验证一种分析方法，该方法应用 Box-Behnken 实验设计并使用高效液相色谱法，能够同时定量包含药物赋形剂的基质中的洗必太和百里酚。优化后，流动相为甲醇和0.03 M磷酸二氢钠缓冲液（60:40），固定相为0.4%三乙胺和辛基硅烷。即使存在氯己定和百里酚降解产物，该方法也被证明具有选择性。对于氯己定，该方法在 4.8 至 19.2 µg/mL 范围内呈线性，对于百里酚，在 8.0 至 32.0 µg/mL 范围内呈线性。准确度接近 100%，精度评估产生的系数变异值 <5%。该方法基于 Box-Behnken 设计，非常稳健，因此经过验证，可协助涉及这些活性药物成分的质量控制过程。