Zhang Yujie, Cao Jingjie, Su Jiahan, He Tingting, Wang Qianru, Wei Feng, Guo Xin, Mei Qibing, Zeng Jing
School of Pharmacy, Southwest Medical University, Luzhou 646000, China.
Shanghai Tonglian Pharmaceutical Co., Ltd., Shanghai 201611, China.
Molecules. 2024 Feb 28;29(5):1037. doi: 10.3390/molecules29051037.
Bitespiramycin, has been shown to have a therapeutic effect against respiratory tract inflammation, including a potential effect against COVID-19. A current clinical trial in China showed that bitespiramycin was an effective treatment for severe pneumonia and intracranial infection. However, there is lack of an analytical method to elucidate the distribution of bitespiramycin. In this study, a highly sensitive, rapid and reliable UPLC-MS/MS method was developed to comprehensively characterize the bitespiramycin distribution in various bio-samples, which is significantly improved upon the published work. A rapid sample preparation method was developed by using -butanol as the solvent to extract bitespiramycin from different bio-samples. The extract was then directly analyzed by UPLC-MS/MS coupled with an alkaline-resistant column after centrifugation which avoids the time-consuming concentration process under nitrogen and redissolution. The method was employed to accurately quantify bitespiramycin and its metabolites in rat plasma, tissues, and human cerebrospinal fluid. Notably, the presence of bitespiramycin and its metabolites was identified for the first time in various rat organs including brain, testis, bladder and prostate as well as in human cerebrospinal fluid. This newly developed approach shows great promise for drug distribution assays including other antibiotics and can help elucidate the ADME of bitespiramycin.
必特螺旋霉素已被证明对呼吸道炎症具有治疗作用，包括对新型冠状病毒肺炎可能有疗效。中国目前的一项临床试验表明，必特螺旋霉素是治疗重症肺炎和颅内感染的有效药物。然而，缺乏一种分析方法来阐明必特螺旋霉素的分布情况。在本研究中，开发了一种高灵敏度、快速且可靠的超高效液相色谱-串联质谱法（UPLC-MS/MS），以全面表征必特螺旋霉素在各种生物样品中的分布，这比已发表的研究有显著改进。通过使用正丁醇作为溶剂，开发了一种快速样品制备方法，用于从不同生物样品中提取必特螺旋霉素。提取物经离心后，直接用UPLC-MS/MS结合耐碱柱进行分析，避免了氮气吹干浓缩和重新溶解这一耗时的过程。该方法用于准确测定大鼠血浆、组织和人脑脊液中必特螺旋霉素及其代谢物的含量。值得注意的是，首次在大鼠的包括脑、睾丸、膀胱和前列腺在内的各种器官以及人脑脊液中鉴定出必特螺旋霉素及其代谢物的存在。这种新开发的方法在包括其他抗生素在内的药物分布测定中显示出巨大潜力，并有助于阐明必特螺旋霉素的吸收、分布、代谢和排泄情况。
