a Investigative Safety and Drug Metabolism , GlaxoSmithKline R&D , Ware, Hertfordshire , UK.
b Bioimaging , GlaxoSmithKline R&D , Stevenage, Hertfordshire , UK.
Biomarkers. 2019 Mar;24(2):131-133. doi: 10.1080/1354750X.2018.1514657. Epub 2018 Oct 25.
Mupirocin (Bactroban) is widely prescribed for intra-nasal decolonisation of MRSA for in-patients awaiting surgery or self-medicated for out-patients although adherence for the latter is not monitored. Non-adherence is a widespread pharmaceutical problem but could encourage selection of antibiotic resistance. Mupirocin is only a topical antibiotic because it decomposes in stomach acidity to monic acid A, but this has not previously been exploited as a biomarker for clinical intra-nasal medication.
Urine from three catheterised patients in two London hospitals during and after mupirocin medication, was passed through Waters Oasis cartridges to isolate organic acids. Sensitive LC-MS-MS analysis for monic acid A in methanolic eluate has been developed to identify ∼10 pg.
Monic acid A was quantified in all samples from one patient, translating into 6-46 ng from 12 mg mupirocin, assuming 1 L daily urine output. However, no urinary monic acid A was detected for two other patients.
Consistent occurrence of monic acid A in urine of one mupirocin patient shows for the first time that antibiotic distribution across nasal mucous membranes had generally been maintained during medication. In contrast, consistent absence in the two other patients requires wider study in hospital.
莫匹罗星(百多邦)被广泛用于住院患者手术前或门诊患者自行鼻腔去定植耐甲氧西林金黄色葡萄球菌(MRSA),尽管后者的用药依从性并未得到监测。不依从是一个普遍存在的药物问题,但它可能会鼓励抗生素耐药性的选择。莫匹罗星只是一种局部用抗生素,因为它在胃酸中分解为单羧酸 A,但这一点以前并没有被用作临床鼻腔内用药的生物标志物。
在伦敦的两家医院,对正在接受莫匹罗星治疗和治疗后的 3 名导尿患者的尿液进行检测,通过 Waters Oasis 小柱对有机酸进行分离。开发了用于甲醇洗脱液中单羧酸 A 的灵敏 LC-MS-MS 分析方法,以鉴定出约 10pg 的单羧酸 A。
一名患者的所有样本中都检测到了单羧酸 A,假设每天的尿液量为 1 升,从 12mg 的莫匹罗星中转化出 6-46ng 的单羧酸 A。然而,另外两名患者的尿液中均未检测到单羧酸 A。
一名莫匹罗星患者尿液中持续出现单羧酸 A,这首次表明抗生素在用药期间通常能在鼻腔黏膜中分布。相比之下,另外两名患者的尿液中持续缺乏单羧酸 A,需要在医院中进行更广泛的研究。