【摘要】：結(jié)核病是一種古老的傳染病。近年來(lái),在世界范圍內(nèi)結(jié)核發(fā)病率呈上升趨勢(shì),給人類(lèi)健康帶來(lái)了巨大的威脅。目前我們常用的一線抗結(jié)核藥物有很多種,由于各種藥物對(duì)結(jié)核桿菌的殺傷力不同,所以在臨床上通常聯(lián)合使用幾種藥物,這樣才能更有效地殺死結(jié)核桿菌。但各種藥物的聯(lián)合應(yīng)用會(huì)帶來(lái)許多不良反應(yīng)和結(jié)核菌的耐藥性,這使得臨床醫(yī)生很難把握藥物的使用劑量。如何應(yīng)用恰當(dāng)?shù)膭┝窟_(dá)到最好的治療效果,將不良反應(yīng)和結(jié)核菌的耐藥性降至最低,對(duì)藥師和臨床醫(yī)師都是一個(gè)挑戰(zhàn)。目前臨床上通常應(yīng)用HPLC-ELSD法和反相高效液相色譜法來(lái)測(cè)定抗結(jié)核藥的血藥濃度,對(duì)臨床醫(yī)生調(diào)整抗菌藥物劑量有一定幫助。但此類(lèi)方法最多只能同時(shí)檢測(cè)到四種抗結(jié)核藥物,而且成本較高,分析時(shí)間長(zhǎng),敏感性不夠,其臨床應(yīng)用價(jià)值有限。為了解決這一難題,本研究采用UPLC-MS/MS法對(duì)患者抗結(jié)核藥物血藥濃度的進(jìn)行測(cè)定,此方法成本較低、分析時(shí)間短,敏感性高,并可同時(shí)檢測(cè)人血漿中乙胺丁醇(EMB)、異煙肼(INH)、吡嗪酰胺(PZA)、利福平、利福噴丁、利福布汀6種抗結(jié)核藥物的血藥濃度,有望為臨床醫(yī)生調(diào)整抗結(jié)核藥物劑量提供更加可靠的依據(jù)。目的:評(píng)價(jià)UPLC-MS/MS法對(duì)于檢測(cè)人類(lèi)血漿中抗結(jié)核藥血藥濃度的價(jià)值,為臨床醫(yī)生調(diào)整抗結(jié)核藥物劑量提供可靠的依據(jù)。方法:利用蛋白沉淀法將被分析物與生物基質(zhì)分離,Waters ACQUITY UPLC HSS T3(1.8μm,2.1×100 mm)色譜柱進(jìn)行色譜分離,采用乙腈-15 m M甲酸銨-0.05%甲酸梯度洗脫,流速為0.2 m L/min,柱溫:40℃,進(jìn)樣量:5μL。并采用ESI源正離子模式,多反應(yīng)監(jiān)測(cè)進(jìn)行測(cè)定。結(jié)果:乙胺丁醇、異煙肼、吡嗪酰胺、利福平、利福噴丁、利福布汀分別在0.05~5μg/m L、0.1-10μg/m L、0.2-20μg/m L、0.05-10μg/m L、0.05-10μg/m L、0.05-5μg/m L范圍內(nèi)線性關(guān)系良好,相關(guān)系數(shù)均大于0.991。除吡嗪酰胺在低濃度點(diǎn)的日間精密度小于15.4%,其它藥物低、中、高3個(gè)濃度的日內(nèi)和日間精密度RSD均小于15%,準(zhǔn)確度為88.1%~109.1%,準(zhǔn)確度良好。結(jié)論:UPLC-MS/MS法操作簡(jiǎn)單、快速,靈敏度高,線性范圍寬,可同時(shí)對(duì)6種抗結(jié)核藥物進(jìn)行檢測(cè),一步完成,減少了分析成本,可為臨床醫(yī)生調(diào)整抗結(jié)核藥物劑量提供重要依據(jù),對(duì)結(jié)核病患者的合理用藥具有重要意義。
[Abstract]:Tuberculosis is an ancient infectious disease. In recent years, the incidence of tuberculosis in the world is on the rise, which poses a great threat to human health. At present, there are many kinds of first-line antituberculotic drugs. Because of the different killing power of various drugs to tuberculosis bacilli, we usually use several drugs together in clinic, so we can kill tuberculosis bacillus more effectively. However, combined use of various drugs will lead to many adverse reactions and drug resistance of tuberculous bacteria, which makes it difficult for clinicians to grasp the dosage of drugs used. It is a challenge for pharmacists and clinicians to use the appropriate dose to achieve the best therapeutic effect and to minimize adverse reactions and drug resistance of tuberculous bacteria. At present, HPLC-ELSD method and RP-HPLC are usually used to determine the concentration of antituberculotic drugs in blood, which is helpful for clinicians to adjust the dosage of antimicrobial agents. However, this method can only detect four antituberculous drugs at the same time, and the cost is high, the analysis time is long, the sensitivity is not enough, and its clinical application value is limited. In order to solve this problem, UPLC-MS/MS method was used to determine the blood concentration of antituberculotic drugs in patients. This method has the advantages of low cost, short analysis time and high sensitivity. The plasma concentrations of ethambutanol (EMB), isoniazid (INH), pyrazinamide (PZA), rifampicin rifambutin and rifambutin in human plasma may provide a more reliable basis for clinicians to adjust the dosage of antituberculosis drugs. Objective: to evaluate the value of UPLC-MS/MS method in detecting the concentration of antituberculous drugs in human plasma and to provide reliable basis for clinicians to adjust the dosage of antituberculous drugs. Methods: Waters ACQUITY UPLC HSS T3 (1.8 渭 m ~ (2.1 脳 100mm) column was separated by protein precipitation method. Acetonitrile -15 mm ammonium formate was eluted with gradient of 0.05% formic acid, flow rate was 0.2 mL / min, column temperature was 40 鈩，

本文編號(hào)：2175919