Development of a detection assay and validation method for a small molecule antimicrobial unstable in biological samples

多年来，人们已经认识到，存在持续存在的细菌感染，并且对防腐剂和抗生素治疗无效。抗生素耐药性目前是对人类健康的最大威胁之一，因为对已知抗生素产生耐药性的病原体越来越多，而且到目前为止，还无法发现新的抗药性来抵消获得性耐药性。因此，印木生物技术正在通过开发一流的合成抗微生物分子来应对这一世界健康危机，这些分子将被用作增强抗生素功效的辅助剂。印木生物技术在生产大蒜衍生化合物方面拥有丰富的经验，这些化合物以其抗菌活性而闻名。我们在有机硫化学方面的领先专业知识使我们能够识别出许多具有高抗菌活性的合成化合物，这些化合物在杀死微生物细胞方面与抗生素和防腐剂具有协同作用。这导致了感染的更快和更有效的解决，减少了它的扩散和扩散到其他解剖位置。现在，我们选择的候选药物进入了临床前开发，我们遇到了一个分析挑战，即无法检测和量化血液和血浆等生物样本中的分子。这给这种有希望的化合物进一步进入临床带来了极大的障碍，因为我们无法进行所需的监管药理学、药代动力学和毒理学安全性研究。Neem已经多次尝试使用LC-MS在内部解决这一分析问题，并外包了两个CRO来开发和验证我们化合物的检测方法，这两个方法都不成功，而且成本高昂。LGC是英国指定的化学和生物分析测量研究所，跨几个部门开展工作。在分析化学和首席科学家质谱学专家克里斯·霍普利的领导下，LGC的团队拥有许多仪器平台和技术，可以为生物基质中的新目标化合物开发方法。重要的是，一旦开发出来，这种方法可以很容易地转化为商业服务，用于我们选定的和Neem Biotech开发的所有未来有机硫化合物资产的成功临床前研究。

For many years it has been recognised that there are bacterial infections that persist and are refractory to treatment with antiseptics and antibiotics. Antibiotic resistance is currently one of the highest threats to human health, given the increasing number of pathogens that develop resistance to known antibiotics as well as the inability, thus far, to discover new ones to offset acquired resistance. Neem Biotech is thus responding to the this world health crisis through the development of first-in-class synthetic anti-microbial molecules to be used as adjunctive agents in potentiating antibiotic efficacy. Neem Biotech has extensive experience in producing garlic-derived compounds known for their antimicrobial activities. Our leading expertise in organosulphur chemistry has allowed us to identify a number of synthetic compounds with high antimicrobial activities and that synergise with antibiotics and antiseptics in microbial cells killing. This results in the more rapid and efficacious resolution of infection, reducing its spread and dissemination to other anatomical locations.Having now progressed our selected drug candidate into preclinical development, we have encountered an analytical challenge, namely, the inability to detect and quantify our molecule in biological samples such as blood and plasma. This poses extraordinary barriers in taking this promising compound further into the clinic since we are unable to undertake the required regulatory pharmacological, phamacokinetic and toxicology safety studies.Neem has made several attempts to resolve this analytical problem in-house using LC-MS and has outsourced two CRO's to develop and validate detection methods for our compound, both of which were unsuccessful and costly.LGC is the designated institute for Chemical and Bio-Analytical measurement in the UK, working across several sectors. Led by Chris Hopley, an expert in analytical chemistry and Principal Scientist Mass Spectrometry, the group at LGC has a number of instrument platforms and technologies to develop methods for novel target compounds in biological matrices. Importantly, once developed, this method can be easily transferred to a commercial service towards the successful preclinical studies of our selected and all future organosulphur compound assets developed at Neem Biotech.