场解吸质谱——Ⅱ.氨基糖甙类

使用电子轰击离子化方法研究氨基糖甙类是不理想的。本文报道用场解吸(简称FD)技术获得的十一个氨基糖甙类的谱图。结果表明谱图不仅给出强的M+H峰,而且还显示出反映氨基糖甙序列的特征碎片。本文还讨论了它们的裂解特点和获得谱图的有关实验技术。     

氨基糖甙类抗生素不良反应

氨基糖甙类抗生素系指分子结构中含有1个氨基醇环和1个或多个氨基糖分子,由配糖链相联接的一类药物。对多数需氧革兰阴性杆菌、金黄色葡萄球菌以及结核分枝杆菌有较强的抗菌活性,价格便宜,故在肺部感染中一直占有较重要的地位。对结核病氨基糖甙类抗生素是首选药物。但是其存在剂量依赖性的毒性,临床应用受到一定限制。     

氨基糖甙类抗生素耳毒性研究进展

<正> 氨基糖甙类抗生素应用于临床已四十多年,这类抗生素为人类抵抗疾病所起的作用早已广为人知。但人们对其引起耳、肾等毒性的重视程度还不够。 据对药物性耳聋患者调查发现,83％是由氨基糖甙类药物引起。有关学者还对北京市四所聋哑学校、北京市耳鼻喉科研究所聋哑门诊儿童及两所工厂的聋哑青年工人进行了调查,调查对象共1039例。其中男554例(53.5％).女485例(46.7％)。致聋原因:药物(小儿应用氨基糖甙类抗生素)618人     

氨基糖甙类抗生素用药方案

氨基糖甙类抗生素用药方案孙昕，王睿（中国人民解放军总医院临床药理研究室北京１００８５３）氨基糖甙类抗生素是广谱抗生素，但因耳、肾毒性较大，限制了它的应用。近年来通过对用药方案的研究，发挥其抗菌优势，降低不良反应。１－日一次给药方案的设想１．１一日一次...     

氨基糖甙类抗生素不良反应探讨

随着抗生素的广泛使用,耐药菌株已成为引起临床感染较为常见的病原菌。一些专家提出抗生素循环（轮换）用药策略和策略性换药,使得氨基糖甙类抗生素对很多耐药菌株敏感。然而,该类药物的治疗浓度范围窄,不良反应较常见,其中有些是不可逆毒性,这是限制它在临床广泛使用的主要原因。为合理的使用该药物,本文重点介绍氨基糖甙类抗生素的不良反应及其防治对策。     

氨基糖甙类的耳毒性及其防治

氨基糖甙类是临床上最常用的一类主要作用于革兰阴性菌的抗生素,也是最易发生耳毒性的一类药物,如链霉素、卡那霉素、新霉素等。本文仅综述其耳毒性特点及防治措施。1 耳毒性特点:(1)发生率高:氨基糖甙类的耳毒性,包括对前庭神经和耳蜗神经的损害。前者发生较早,通常在2～4周发生,主要表现为眩晕、恶心、呕吐、共济失调等,及时停药可恢复;后者发生较晚,多数在1～3个月出现,主要表现为耳鸣、耳聋。据统计全国1770万聋人中,有300万为应用耳毒性药物引起,足见其危害。(2)     

氨基糖甙类：另一前景展望

尽管有几种新类型的抗菌药物用一进入, 氨基糖苷类仍被认为是处理严重革兰氏阴性菌引起的脓毒症的第一线治疗药物，限制氨基糖苷类抗生素使用的主要障碍是引起药源性耳中毒辣和肾中毒的可能性。本文评述了用于确诊氨基糖甙类引起的肾毒性和耳毒性的定义和这些不良反应的临床意义，同时也集中讲座了治疗药物监测中遇到的实际问题，结论是：氨基糖甙类抗生素仍色色是治疗严重感染的一种有效手段，如果选用时认真对待，那治疗上的益处要超过中毒的危险。     

表面辅助激光解吸/离子化质谱技术用于药物和代谢物分析（英文）

表面辅助激光解吸/离子化质谱(SALDI-MS)技术是利用无机纳米材料为基质,以促进待测物的解吸附和离子化。对比传统的基质辅助激光解吸/离子化质谱(MALDI-MS)技术,SALDI-MS具有质谱信号在低质量端干扰小、重现性好、耐盐度高等优点,非常适合于小分子化合物的分析。近年来,研究人员开发了一系列纳米材料,成功地将该技术应用于小分子药物和代谢物分析领域,包括药物筛查和定量、药物递送、代谢物轮廓分析、生物标志物发现等。本综述总结了最新发展的SALDI-MS基质材料(金属类材料、碳材料、硅材料和有机框架纳米材料)在这个领域的应用。此外,文中对SALDI-MS技术进行了展望,以期能进一步促进该技术的发展。     

Direct analysis of cannabis samples by desorption atmospheric pressure photoionization‐mass spectrometry

Fast analysis of cannabis samples without prior sample preparation or chromatography was performed using desorption atmospheric pressure photoionization‐mass spectrometry (DAPPI‐MS). The MS² spectra of the molecular ions of tetrahydrocannabinol (THC) and cannabidiol (CBD) formed in DAPPI‐MS showed distinct product ions, unlike the protonated molecules formed with other ambient mass spectrometry techniques, making possible the reliable identification of THC from cannabis samples. Copyright © 2012 John Wiley & Sons, Ltd.     

Rapid identification of herbal toxins using electrospray laser desorption ionization mass spectrometry for emergency care

The unintentional ingestion of toxic compounds in herbs is not uncommon in many parts of the world. To provide timely and life-saving care in the emergency department, it is essential to develop a point-of-care analytical method that can rapidly identify these toxins in herbs. Since electrospray laser desorption ionization mass spectrometry (ELDI/MS) has been successfully used to characterize non-volatile chemical compounds without sample preparation, it was used to identify toxic herbal compounds in this study. The herbal toxins were collected either by sweeping a metallic probe across the surface of a freshly cut herb section or by directly sampling extracts of ground herbal powder. The analytes on the probe were then desorbed, ionized and detected using ELDI/MS, wherein analysis of the herbal toxins was completed within 30 s. This approach allows for the rapid morphological recognition of herbs and early point-of-care identification of herbal toxins for emergency management and is promising in providing important toxicological information to ensure appropriate medical treatment.     

Direct and rapid characterization of illicit drugs in adulterated samples using thermal desorption electrospray ionization mass spectrometry

Foods and drinks have been adulterated with illicit drugs to facilitate criminal activities. Unfortunately, conventional analytical methods are incapable of rapidly characterizing these drugs in samples, as serious interferences from sample matrices must be removed through tedious and time-consuming pretreatment. Ambient ionization mass spectrometry (AMS) generally does not require sample pretreatment and is thus a suitable tool for directly and rapidly detecting illicit drugs in samples in different physical states. In this study, thermal desorption electrospray ionization mass spectrometry (TD-ESI/MS), an AMS technique, was utilized to efficiently characterize illicit drugs spiked in samples including drinks, powders, and jelly candies. To perform sensitive analysis, the mass analyzer was operated in multiple reaction monitoring mode to monitor the molecular and fragment ions of the target analytes. The time required to complete a typical TD-ESI/MS analysis was less than 30 s. The limits of detection (LODs) for illicit drugs were found to be 100 ppb in drinks, 100–1000 ppb in instant powders, and 1.3–6.5 ng/mm² on stamp surfaces. FM2 and nitrazepam laced in the inner layer of a jelly candy were detected by TD-ESI/MS, showcasing the advantage of the technique for direct and rapid analysis as opposed to conventional methods.     

Capillary electrophoresis to characterize ricin and its subunits with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

Capillary electrophoresis (CE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) have been employed as highly efficient methods to characterize ricin, its subunits, and the chemically deglycosylated forms. As a CE method, sodium dodecyl sulfate-capillary gel electrophoresis (SDS-CGE) was used because of its merit over the conventional slab gel techniques. SDS-CGE showed higher resolution capability over other analytical tools in the analysis of the ricin mixture as well as in each of its purified forms. The high resolution was considered to be a result of the presence of carbohydrates on ricin subunits, and this property was useful for identifying the native ricin or its A chain from their chemically deglycosylated forms. However, this method exhibited an overestimation of the molecular mass due to the carbohydrate moieties on ricin subunits, and the inaccuracies were observed to be dependent on the carbohydrate content of the subunits. The exact molecular masses were measured by MALDI-TOF MS, and the results were almost consistent with the expected values. This study clearly illustrates the usefulness and necessity of complementary use of two powerful analytical techniques to characterize ricin and its subunits in a various research fields such as poisoning and immunotoxin research.     

表面加强激光解析电离-飞行时间-质谱技术在急性重症胰腺炎预后相关蛋白质谱检测中的应用

目的 应用蛋白芯片表面加强激光解析电离-飞行时间-质谱(SELDI-TOF-MS)技术检测急性重症胰腺炎不同预后相关蛋白质谱,探讨急性重症胰腺炎轻重程度及预后评估的新方法.方法 用SELDI-TOF-MS方法检测浙江省人民医院2008年3月至2010年10月23例急性重症胰腺炎患者的蛋白质谱,按是否发生器官功能衰竭、胰腺脓肿、腹内压异常、死亡将全部患者分组进行蛋白指纹图谱比较.结果 蛋白质峰谱特征显示,在1094 u、2751 u、5904 u处并发胰腺脓肿(13例)的重症胰腺炎患者峰值(13.21±3.73,45.62±10.31,48.37±9.24)明显高于未并发胰腺脓肿组(70例)(4.33±1.79,8.87±3.21,4.45±1.59),差异有统计学意义,均P<0.05.在635 u并发器官功能衰竭组(11例)峰值(8.56±3.21)明显低于未并发器官功能衰竭组(12例)(37.82±12.65);而在4103 u、4187 u处并发器官功能衰竭组(21.63±8.23.9.81±2.32)峰值则高于未并发器官功能衰竭组(3.32±1.29,1.14±0.49).在4173 u处并发腹内压增高组(10例)峰值(8.94±3.58)明显高于无腹内压增高组(13例)(1.97±0.73);而在5635 u处并发腹内压增高组峰值(0.62±0.23)则低于无腹内压增高组(15.78±6.34).2例死亡患者蛋白指纹表现为血清蛋白全面合成功能减退,峰值降低.结论 蛋白指纹图谱技术可筛选出有意义的生物标记蛋白,为急性重症胰腺炎并发症的早期诊断与治疗提供了新的路径,对急性重症胰腺炎预后评估具有重要意义.

Abstract：

Objective To analyze the serum proteomic pattern in different severe acute pancreatitis complication by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) for evaluating the stage and prognosis of severe acute pancreatitis. Methods Serum samples were collected from 23 severe a-cute pancreatitis. Serum from organ nonfunction, pancreatic abscess, intra-abdominal hypertension and death were profiled using WCX Proteinchip and analyzed by mass spectrometry. Results Protein peak in the spectrum characteristics showed that at 1094u, 2751u, 5904u, the peak value of concurrent pancreas abscess pancreatitis [13.21 ± 3.73, 45.62±10.31, 48.37±9.24] were significantly higher than those in none-pancreas abscess group [4.33 ± 1.79, 8. 87 ±3.21, 4.45 ±1.59] (P<0.05). At 635u, the peak value of concurrent organ failure group(8.56 ± 3.21) was obviously lower than those in none-organ failure group(37.82 ± 12.65). At 4103u and 4187u, the peak value of in complicated organ failure group [21.63 ±8.23, 9.81±2.32] were higher than those in none-organ failure group [3.32±1.29, 1.14 ±0.49], At4173u, the peak value of concurrent increased intraabdominal pressure group(8.94 ±3.58) was significantly higher than that in none-intraabdominal pressure group(1.97 ±0. 73) , while at 5635u the peak value of concurrent increased intraabdominal pressure groups ( 0. 62 ± 0. 23 ) was lower than that without intraabdominal pressure group (15.78 ±6.34). Two cases died. Protein fingerprints showed that overall serum protein composite function dropped and the peak value reduced. Conclusion Proteomic technology can significantly identify novel significant biomarkers in the serum, which provides a new way to diagnose and treat the different complication of severe acute pancreatitis early and has clinical significance in evaluating the prognosis of severe acute pancreatitis.     

基质辅助激光解析电离飞行时间质谱检测耐甲氧西林金黄色葡萄球菌δ-毒素的应用

目的 本研究采用基质辅助激光解析电离飞行时间质谱(MALDI-TOF MS)检测δ-毒素,评估其在耐甲氧西林金黄色葡萄球菌(MRSA)的分型和毒力表达中的作用。方法 使用Bruker microflex MALDI-TOF仪器,采集2000~20000Da质量范围内,以正线性模式采集图谱,使用仪器配套的MALDI Biotyper 2.0软件分析MRSA菌株的原始图谱,产生的峰列表直接使用flexAnalysis、clinProTools3.0软件分析。结果 本研究中共检测83株MRSA,共有39(47.0%)株MRSA检出(3005±5)m/z信号峰,其中HA-MRSA 19(22.9%)株,CA-MRSA 20(26.5%)株,P=0.766,两者之间无显著性差异;33(39.8%)株MRSA检出(3035±5)m/z信号峰,其中HA-MRSA 9 (10.8%)株,CA-MRSA 24(28.9%)株,P=0.003,两者之间有显著性差异;11(13.%)株MRSA既未检出(3005±5)m/z信号峰也未检出(3035±5)m/z信号峰,全部为HA-MRSA菌株。spa分型中检出(3005±5)m/z信号峰,15(18.1%)株为t062型,8株为t015(9.6%)型,4株为t030(4.8%)株,P=0,有显著性差异;检出(3035±5)m/z信号峰,31(37.3%)株为t437型,2(2.4%)株t8660型,P=0,有显著性差异;(3035±5)m/z作为spa t437型特征信号ROC曲线下面积0.89,P=0。11株未检出δ-毒素,6株分离自骨关节标本,3株分离自呼吸道标本,1株分离自慢性溃疡的分泌物标本,1株分离自血液;在血平板的菌落特征,6株MRSA菌落形态发生改变,5株菌落形态正常。结论 MALDI-TOF MS使用常规方法即可快速检测MRSA的δ-毒素,其质谱峰为(3005±5)m/z和(3035±5)m/z两种;(3035±5)m/z是δ-毒素的同基因变异体(HldG10S)的质谱峰,该峰可快速鉴别spa t437型;不产生δ-毒素的菌株是agr调控系统失调的表现,与慢性感染、小菌落形成、无明显β-溶血有关。