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，并且用防腐剂和抗生素治疗是难治性的。抗生素耐药性目前是对人类健康的最大威胁之一，因为越来越多的病原体对已知抗生素产生耐药性，而且迄今为止无法发现新的抗生素来抵消获得性耐药性。因此，印楝生物技术公司通过开发一流的合成抗微生物分子来应对这场世界卫生危机，这些分子被用作增强抗生素功效的辅助剂。Neem Biotech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，并与抗生素和防腐剂协同杀死微生物细胞。这导致更快速和有效的解决感染，减少其扩散和传播到其他解剖位置。在我们选定的候选药物进入临床前开发阶段后，我们遇到了分析方面的挑战，即无法在血液和血浆等生物样品中检测和量化我们的分子。由于我们无法进行必要的药理学、药代动力学和毒理学安全性研究，这给这种有前景的化合物进一步进入临床带来了巨大的障碍。Neem曾多次尝试使用LC-MS在内部解决这个分析问题，并外包了两个CRO来开发和验证我们的化合物的检测方法，但都没有成功且成本高昂。LGC是英国指定的化学和生物分析测量研究所，横跨多个部门。在分析化学专家和质谱首席科学家Chris Hopley的带领下，LGC的团队拥有许多仪器平台和技术来开发生物基质中新型目标化合物的方法。重要的是，一旦开发出来，这种方法可以很容易地转移到商业服务中，以成功地进行我们选择的临床前研究，以及未来在Neem Biotech开发的所有有机硫化合物资产。

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.