本文關鍵詞： 氨基糖苷類抗生素 萬古霉素 治療藥物濃度監(jiān)測 LC-MS/MS CMIA HPLC-UV　出處：《上海師范大學》2017年碩士論文　論文類型：學位論文

【摘要】：氨基糖苷類抗生素如阿米卡星、異帕米星、妥布霉素是治療耐藥革蘭陰性菌感染的的重要抗生素之一,糖肽類抗生素萬古霉素是抗耐甲氧西林金黃色葡萄球菌(MRSA)等耐藥革蘭陽性菌感染的首選抗生素,近年來CHINET耐藥監(jiān)測網結果顯示,該些抗生素仍然對耐藥革蘭陰性菌或耐藥革蘭陽性菌保持良好的敏感率,推薦單藥或聯(lián)合用于耐藥菌引起的嚴重感染。然而該些抗生素主要從腎臟排泄,并有耳腎毒性,藥物療效、毒性均與血藥濃度濃度相關。為提高臨床療效和安全性,國內外的指南均推薦對氨基糖苷類抗生素和萬古霉素進行治療藥物濃度監(jiān)測(Therapeutic Drug Monitoring,TDM)。臨床醫(yī)生可根據監(jiān)測的血藥濃度,結合病人病情等進行個體化給藥劑量的調整,提高該類藥物療效,減少毒副反應的發(fā)生。因而,準確、靈敏的定量分析方法測定該些抗生素在血清(血漿)中的藥物濃度很有必要。目前,氨基糖苷類抗生素和萬古霉素治療藥物濃度監(jiān)測的分析方法主要為免疫分析法。阿米卡星、妥布霉素、異帕米星在國外已有商品化的免疫試劑盒用于其血藥濃度監(jiān)測,但在中國尚未進行臨床注冊,不能在臨床使用,使得該類藥物在國內臨床TDM的開展受到了限制。萬古霉素在國內有免疫方法、高效液相法和液質聯(lián)用法等測定患者血樣中萬古霉素濃度,近期國外文獻報道不同廠家生產的儀器、相同廠家生產的儀器的定量下限、測得藥物濃度均存在一定差異。此將對萬古霉素的TDM方法準確性帶來挑戰(zhàn)。大樣本數據量下不同分析方法間的檢測差異及對臨床醫(yī)生調整給藥方案判斷的影響,目前國內尚無相關報道。本課題研究將分成兩部分:第一部分:氨基糖苷類抗生素阿米卡星、異帕米星、妥布霉素LC-MS/MS法建立及臨床樣本監(jiān)測本課題建立了用于三種氨基糖苷類抗生素治療藥物濃度監(jiān)測分析的LC-MS/MS法,對方法的特異性、精密度與準確度、基質效應與回收率、標準曲線與定量下限、樣品放置穩(wěn)定性、自動進樣器穩(wěn)定性、進樣重復性、殘留效應、交互作用等進行了考察。收集、測定了接受阿米卡星治療的革蘭陰性菌感染患者的樣本,首次了解中國患者用藥后的血藥谷濃度、峰濃度水平,為開展中國患者革蘭陰性菌感染患者阿米卡星治療藥物濃度監(jiān)測臨床觀察研究提供了參考。第二部分:三種萬古霉素血藥濃度檢測方法的比較及對臨床TDM結果影響的分析本課題基于以前的實驗基礎,考察了大樣本數據量下常見的三種萬古霉素血藥濃度分析方法測定結果的相關性及差異,并分析了不同檢測方法下臨床給藥方案調整判斷的差異,為TDM分析方法的選擇提供參考,進一步保障萬古霉素TDM分析結果的準確性。
[Abstract]:Aminoglycoside antibiotics such as amikacin, isopamicin and tobramycin are one of the important antibiotics for the treatment of drug-resistant gram-negative bacteria. Vancomycin, a glycopeptide antibiotic, is the first choice of antibiotics for resistant gram-positive bacteria such as methicillin-resistant Staphylococcus aureus (MRSA). In recent years, the results of CHINET resistance monitoring network show that vancomycin is the first choice of antibiotics. These antibiotics remain highly sensitive to the resistant or resistant gram-positive bacteria and are recommended for single or combined use in severe infections caused by drug-resistant bacteria. However, these antibiotics are mainly excreted from the kidneys. The otorenal toxicity, drug efficacy and toxicity were all related to the concentration of blood drug. In order to improve the clinical efficacy and safety. Both domestic and foreign guidelines recommend therapeutic concentration monitoring of aminoglycoside antibiotics and vancomycin for Therapeutic Drug Monitoring. The clinicians can adjust the dosage of individualized medicine according to the concentration of blood drug and the patient's condition, improve the curative effect of this kind of drug, and reduce the occurrence of side effects. Therefore, it is accurate. A sensitive quantitative method is necessary to determine the concentration of these antibiotics in serum (plasma). Aminoglycoside antibiotics and vancomycin treatment drug concentration monitoring methods are mainly immunoassay. Amikacin, tobramycin. Isoparmicin has been commercially available in foreign countries for monitoring its blood concentration, but it has not been registered clinically in China and cannot be used in clinical use. Vancomycin has been used in China to determine the concentration of vancomycin in blood samples by high performance liquid chromatography (HPLC) and liquid / mass spectrometry (HPLC). It is reported in recent foreign literature that the quantitative lower limit of the instruments produced by different manufacturers and the instruments produced by the same manufacturers. This will challenge the veracity of vancomycin TDM method. The difference between different analytical methods in large sample data and its influence on clinicians' judgment of adjusting drug delivery plan. Ring. At present, there are no related reports in China. This research will be divided into two parts: the first part: aminoglycoside antibiotics amikacin, isopamicin. Establishment of tobramycin LC-MS/MS method and clinical sample monitoring the LC-MS/MS method for monitoring the concentration of three aminoglycoside antibiotics was established. Precision and accuracy, matrix effect and recovery, standard curve and lower limit of quantification, stability of sample placement, stability of automatic sampler, repeatability of injection, residual effect and interaction were investigated. Samples of patients with Gram-negative bacilli infection treated with amikacin were measured, and the serum concentration and peak concentration of Gram-negative bacteria in Chinese patients were investigated for the first time. It provides a reference for clinical observation and study on the concentration monitoring of amikacin in Chinese patients with Gram-negative bacilli infection. Part two:. Comparison of three methods for determination of vancomycin concentration and analysis of the effect on clinical TDM results this subject is based on the previous experimental basis. The correlation and difference of three common methods for determination of vancomycin concentration in large sample data were investigated, and the differences of the adjustment and judgment of clinical administration schemes under different detection methods were analyzed. To provide a reference for the selection of TDM analysis methods and to further ensure the accuracy of vancomycin TDM analysis results.
【學位授予單位】：上海師范大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R969

【參考文獻】

相關期刊論文 前10條

1 張聰;梅清華;盧慧勤;林壯民;梁金成;;液相色譜-串聯(lián)質譜法測定人血漿中阿米卡星、地塞米松和利巴韋林的濃度[J];中國藥學雜志;2016年11期

2 王偉;;血清標本發(fā)生溶血和脂血對生化檢驗結果的影響分析[J];當代醫(yī)藥論叢;2015年19期

3 胡付品;朱德妹;汪復;蔣曉飛;徐英春;張小江;張朝霞;季萍;謝軼;康梅;王傳清;王愛敏;徐元宏;沈繼錄;孫自鏞;陳中舉;倪語星;孫景勇;褚云卓;田素飛;胡志東;李金;俞云松;林潔;單斌;杜艷;韓艷秋;郭素芳;魏蓮花;吳玲;張泓;孔菁;胡云建;艾效曼;卓超;蘇丹虹;;2014年CHINET中國細菌耐藥性監(jiān)測[J];中國感染與化療雜志;2015年05期

4 吳琳羚;畢亞萍;李丹;劉莎;李瑾穎;付敏;王高軍;劉佳明;;微生物學檢測技術在食品抗生素殘留檢測的研究應用[J];中國微生態(tài)學雜志;2014年05期

5 姜艷彬;單吉浩;王瑩;蔡英華;田亞平;;LC-MS/MS技術在藥物代謝研究中的應用進展[J];藥物分析雜志;2014年03期

6 龍森;王澤民;何敏;;抗菌藥物使用強度分析與探討[J];中華醫(yī)院感染學雜志;2013年24期

7 張麗;石小楓;郝榮濤;劉毅;;不合理使用抗生素致真菌性食管炎2例[J];重慶醫(yī)學;2013年30期

8 曹鈺然;郁繼誠;陳淵成;武曉捷;張菁;施耀國;;萬古霉素室間質量控制結果的評價[J];中國感染與化療雜志;2013年03期

9 武曉捷;董曉易;陳軼堅;張菁;施耀國;吳菊芳;張嬰元;;伏立康唑治療藥物濃度監(jiān)測方法的建立[J];中國感染與化療雜志;2009年02期

10 管華;石茂健;崔亞男;;免疫分析技術研究進展[J];亞太傳統(tǒng)醫(yī)藥;2007年10期

相關會議論文 前1條

1 葉志康;李曉光;翟所迪;;中國萬古霉素治療藥物監(jiān)測現(xiàn)況研究[A];2013年中國臨床藥學學術年會暨第九屆臨床藥師論壇論文集[C];2013年

，

本文編號：1443357