头孢硫脒降解产物的LC-MS分析

目的分析确定头孢硫脒的降解产物。方法用LC—MS分析头孢硫脒长期留存样品和冻干样品的降解情况。结果主要的两个有关物质一为头孢酯脒，二为去乙酰头孢硫脒。结论为头孢硫脒的质量控制和稳定性研究提供了重要依据。     

LC-MS法分析头孢硫脒中的主要杂质

目的对国内四家头孢硫脒制剂产品进行检测,确证超过报告限度(>0.05%)杂质的结构。方法采用HPLC法、LC-MS法及NMR法对头孢硫脒进行了强制降解杂质研究、长期留样杂质研究、杂质谱研究。结果存在四个超过报告限度的杂质,降解杂质为去乙酰头孢硫脒和头孢硫脒内酯,其他杂质为7-溴乙酰胺头孢烷酸(7-BCA)、头孢硫脒Δ2异构体。结论为头孢硫脒的质量控制和稳定性研究提供了重要依据。     

利用LC-MS/MS法快速鉴定盐酸头孢吡肟中的同分异构体杂质

目的建立应用LC-MS/MS技术快速鉴定盐酸头孢吡肟原料药中的同分异构体杂质的方法。方法以乙腈-10 mmol·L^-1乙酸铵(5∶95)为流动相经C₁₈柱分离,通过电喷雾串联质谱在线检测，获得相关的色谱和质谱信息。结果在所建立的条件下，盐酸头孢吡肟及其同分异构体杂质获得有效分离，主成分和其同分异构体杂质的保留时间分别为15.28 min和9.18 min，同时它们的二级质谱产物离子信息及其裂解方式呈现明显的差异。结论本法能快速、准确地分离鉴定盐酸头孢吡肟原料药中的同分异构体杂质，从而可以对其原料药进行质量控制。     

头孢硫脒新杂质的制备及结构解析

目的 对头孢硫脒的氧化杂质和双键转移杂质进行制备和结构分析。方法 用适当的反应方法处理原料，目标杂质用HPLC定位，经分离纯化得到两个杂质的纯品，通过多级质谱和核磁共振确认其结构。结果 对制备得到的两个杂质的结构做了解析，双键转移杂质为6R,7R-3-[(乙酰氧基)甲基)]-7-[α-N,N'-二异丙基脒硫基)乙酰氨基]-8-氧代-5-硫杂-1-氮杂双环[4.2.0]辛-3-烯-2-甲酸内铵盐，氧化杂质为6R,7R-3-[(乙酰氧基)甲基)]-7-[α-(N,N›-二异丙基脒硫基)乙酰氨基]-8-氧代-5-硫杂-1-氮杂双环[4.2.0]辛-2-烯-2-甲酸内铵盐-5-氧化物，并推测出其降解路线。结论 本研究对头孢硫脒原料及其制剂的杂质分析和质量控制有重要参考价值。     

注射用头孢硫脒杂质谱分析及质量控制

摘要：目的 对头孢硫脒原料及制剂中杂质进行定性分析,比较原料晶型的异同。方法 采用HPLC及柱切换HPLCMS 方法对4个厂家头孢硫脒原料以及12个厂家注射用头孢硫脒杂质谱进行分析。采用粉末X-射线衍射方法对原料晶型进行 分析。结果 共检出6种主要杂质,并对杂质的结构及来源进行了分析,确认了关键指针性杂质。测定了不同厂家原料的晶 型。结论 对头孢硫脒杂质以及晶型的分析可用于监控原料及制剂降解情况以及工艺控制的合理性。     

头孢雷特中主要降解产物的结构解析

目的 对头孢雷特中的主要降解产物进行结构解析。方法 采用液质联用技术对2个主要降解产物进行质谱分析,初步确认结构后通过TLC法、制备液相色谱法、化学合成等方法得到头孢雷特中2个未知降解产物单体,并进一步利用核磁共振(NMR)技术、质谱(MS)等进行结构确证。结果 2个主要降解产物分别为5-巯基-1H-四氮唑乙酸和(6R,7R)-7-[[(邻氨甲基苯)乙酰]氨基]-3-羟甲基-8-氧代-5-硫杂-1-氮杂双环[4,2,0]-辛-2-烯-2-甲酸。结论 本研究为头孢雷特工艺生产和贮存条件的选择提供了科学依据。     

头孢硫咪体外抗菌活性测定

目的：评价第一代头孢菌素头孢硫脒对近期从临床分离的致病菌的体外抗菌活性。方法：用对倍稀释法测定头孢硫咪的最小抑菌浓度（ＭＩＣ）并与头孢唑啉、头孢呋辛、头孢他啶体外抗菌活性进行了对比。结果：头孢硫脒对肺炎球菌、化脓性链球菌、ＭＳＳＡ、ＭＳＳＥ和卡他布汉氏菌有较强的抗菌活性。结论：头孢硫脒对Ｇ^＋球菌有较强的抑菌活性和杀菌活性,对肠球菌亦显示有很强的体外抗菌活性。     

头孢硫脒不良反应文献分析及原因探讨

目的：调查分析注射用头孢硫脒近年来的不良反应（ADR）发生情况,探讨ADR发生的原因,为临床合理用药提供指导。方法：检索中国知网（CNKI）、万方医学网数据库中2001-2015年关于头孢硫脒的ADR病例,从ADR发生的人群分布、临床表现等方面进行统计、分析。同时从头孢硫脒的化学结构、与输液配伍的稳定性及降解产物三个方面对头孢硫脒ADR进行原因分析。结果：搜集到符合条件的文献15篇,共有98例患者。9岁以下的儿童共40例,ADR发生率最高。ADR可累及消化系统、神经系统、呼吸系统、循环系统、皮肤及其附件。头孢硫脒与部分输液配伍稳定性较差,随着放置时间的增加,可产生具有过敏源性的杂质,这可能是其ADR发生的原因之一。结论：临床使用头孢硫脒时应监测ADR,ADR发生的原因还需要进一步研究。     

2D-LC-IT-TOF/MS联用Cef-SEC法鉴定注射用头孢硫脒中高分子杂质

目的 建立高效分子排阻色谱法(Cef-SEC)测定头孢硫脒中的聚合物,并用应用在线脱盐-高效液相色谱-离子阱-飞行时间质谱对其聚合物进行结构鉴定。方法 采用WT-Cef-SEC (7.8mm×30.0cm,5μm)色谱柱；流动相为5mmol.L-1磷酸盐缓冲液-乙腈(95: 5)；进样量为20μL；检测波长为254nm； ESI电离源,正离子扫描；主成分自身对照法计算聚合物的含量。结果 在该条件下头孢硫脒峰与聚合物峰分离良好；通过2D-LC-IT-TOF/MS推测出聚合物1为头孢硫脒二聚体,聚合物2为去乙酰头孢硫脒氧化杂质聚合体。结论 本方法适用于注射用头孢硫脒高分子杂质的测定,同时为β-内酰胺类抗生素中聚合物的分离、分析及产品质量提高提供了依据。     

69株革兰阳性球菌对抗菌药物的体外敏感度测定

目的了解抗菌药物对临床常见革兰阳性球菌的体外抗菌活性。方法采用K B法对临床分离得到的69株革兰阳性球菌进行药物敏感性测定。结果革兰阳性球菌对万古霉素的敏感率为100.0%，表皮葡萄球菌对头孢硫脒的敏感率为89.7%，对头孢唑林为84.4%;金黄色葡萄球菌对头孢硫脒的敏感率为95.0%，对头孢唑林为93.5%。肠球菌对头孢硫脒和头孢唑林的敏感率均为50%。结论头孢硫脒对革兰阳性球菌的抗菌活性优于头孢唑林、红霉素、阿奇霉素，仅次于万古霉素。头孢硫脒与头孢唑林对肠球菌的抗菌活性基本相同。     

LC-MS-MS法分析伏立康唑的碱降解产物

目的:建立以液相色谱-串联质谱法快速分析伏立康唑的碱降解产物的方法。方法:借助色谱-串联质谱技术,比较并分析伏立康唑对照品和其碱降解产物的相对分子质量、碎片、光谱特征等信息。结果:伏立康唑与其降解产物能有效分离,2个主要降解产物分别为去4-乙基-5-氟嘧啶的同分异构体。结论:该方法快速、灵敏、专属性强,可用于推测伏立康唑降解产物的结构。     

LC-MS/MS法检测西维来司他原料药中的降解产物

目的：探讨应用液相色谱-串联质谱法（LC-MS/MS）检测西维来司他原料药中的降解产物.方法：以乙腈-水-甲酸（40：60：0.1）为流动相,待测物经Hypersil C18柱分离,电喷雾串联质谱在线检测,获得相关的色谱和质谱信息.结果：在所应用的条件下,西维来司他与其降解产物达到了很好分离,主成分和其降解产物峰的保留时间分别为18.46和3.36min,同时通过两者的质谱特征获得了降解产物的结构信息.结论：所建立的方法能快速、准确地分离鉴定西维来司他原料药中的降解产物,从而可以对其原料药进行质量控制.     

Structural characterization of the oxidative degradation products of an antifungal agent SCH 56592 by LC-NMR and LC-MS

LC-NMR and LC-MS were used to characterize the structures of four major degradation products of SCH 56592, an antifungal drug candidate in clinical trials. These compounds were formed under stress conditions in which the bulk drug substance was heated in air at 150 degrees C for 12 days, and were separated from SCH 56592 as a mixture using a semi-preparative HPLC method. The data from LC-NMR, LC-ESI-MS (electrospray ionization mass spectrometry) and LC-ESI-MS/MS indicate that the oxidation occurred at the piperazine ring in the center of the drug molecule. The structures of the degradation products were determined from the 1H NMR spectra obtained via LC-NMR, which were supported by LC-ESI-MS and LC-ESI-MS/MS analyses. A novel degradation pathway of SCH 56592 was proposed based on these characterized structures.     

Analysis of the degradation compounds of chemical warfare agents using liquid chromatography/mass spectrometry

The analysis of the degradation products of chemical warfare (CW) agents has been a challenge to analysts. The low volatility of these compounds makes them unsuitable for direct gas chromatography analysis without prior derivatization. Lack of a chromophore causes difficulties with classic detection methods after liquid chromatography separation. With the recent development of various interfaces that allow for the introduction of a liquid solvent stream into the mass spectrometer, the task of directly analyzing these compounds has become easier. For this report, we examined three different liquid chromatography/mass spectrometry (LC/MS) interfaces for their suitability for the analysis of CW degradation compounds. The interface types examined were particle beam electron impact ionization (PBI), electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI). Several alkylphosphonates and thiodiglycol analogs that are produced from the degradation of organophosphorus nerve agents and sulfur mustard, respectively, were analyzed using each of the three techniques. Electron impact ionization following gas chromatography or particle beam introduction typically generates very reproducible, library-searchable mass spectra. Most of the CW breakdown compounds examined using the PBI interface did not produce a molecular ion. Despite the lack of a molecular ion, the mass spectra of the various compounds contained enough different structural information from fragment ions for the positive identification of each. The mass spectra generated using ESI are generally limited to protonated molecular ions with little or no fragmentation. For positive identification and confirmation, tandem mass spectrometry techniques quite often must be used. Many of the compounds in this study were characterized by prominent sodiated adducts along with the protonated molecular ion. Methylphosphonic acid produced protonated dimers, trimers, etc. Although the various adduct ions can be used for additional confirmation of the molecular weight of a compound, the adducts also can result in suppression of ionization of the compound and thus reduce sensitivity. Another 'soft' ionization technique that results in abundant protonated molecular ions is APCI. The mass spectra of the breakdown compounds produced using APCI were characterized generally by either a prominent protonated molecular ion or a dehydrated form of it. In addition, a number of structurally significant fragment ions were observed and their relative abundances could be adjusted by altering the APCI conditions. The data presented here indicate that each of the three techniques can be used successfully for direct liquid introduction and analysis of the non-volatile compounds produced from the degradation of CW agents. The mass spectra produced using each technique are quite different and could be utilized as additional confirmation of compound identity.     

Characterization of forced degradation products of toloxatone by LC-ESI-MS/MS

Forced degradation of toloxatone in solutions under basic, acidic, neutral, photo UV–VIS, photo UVC and oxidative stress conditions was investigated and structural elucidation of its degradation products was performed with the use of UHPLC system coupled ESI-Q-TOF mass spectrometer. Eight degradation products were found and their masses and formulas were obtained with high accuracy (0.09–3.79?ppm). The structure of unknown degradation products were elucidated from MS/MS fragmentation spectra of all analyzed compounds. Additionally, whole signals of decomposed substances were compared chemometrically. It was found that toloxatone is fragile towards basic hydrolysis, oxidative conditions and UVC irradiation. Finally, the toxicity of transformation products was computationally evaluated and compared in multivariate manner.     

枳壳化学成分和代谢成分的UPLC-PAD-Q-TOF／MS分析

目的：建立寻找枳壳提取物活性成分的方法。方法：采用超高效液相色谱仪．质谱联用（UPLC-PAD—Q-TOF／MS）方法对枳壳水提液及其入血成分进行分析,通过紫外光谱、质谱数据等对化合物进行解析。结果：从枳壳水提液中鉴定了21个化合物,其中包括12个黄酮苷类化合物,9个多甲基黄酮类化合物;在小鼠血浆中检测到6种原型成分和4种代谢产物。结论：UPLC—PAD—Q—TOF／MS法可用于中药活性成分的鉴定。     

Detection and analysis of the cyanobacterial peptide hepatotoxins microcystin and nodularin using SELDI-TOF mass spectrometry.

Surface-enhanced laser desorption ionization mass spectrometry (SELDI-TOFMS) was used to develop a new and useful method for determination and identification of the cyanobacterial (blue-green algae) toxins: microcystin and nodularin. The technique, combining chromatography and MS, enables microcystin/nodularin capture, purification, analysis, and processing from complex biological mixtures directly onto a hydrophobic chip. Factors affecting ion intensities, including matrix concentration and laser intensity, were investigated to optimize sensitivity of the method. Microcystins and nodularin were analyzed for femtomolar sensitivity (about 2.5 pg microcystin-LR in 2 microl water). Samples of blood sera and liver tissue were spiked with microcystin-LR and analyzed. The detection limit was 1 ng in 2 microl blood sera solution. Reactions of microcystins by compounds containing mercaptan groups, such as dithiothreitol, aminoethanethiol and protein phosphatase 1, were examined on the chip by mass spectrometry. Formation of the microcystin-dithiothreitol conjugate was used to confirm the target compounds. The MS/MS data obtained showed the presence of the microcystin conjugate. The reaction position of the toxin with target compound was confirmed by a series of MS/MS fragment ions. The protein profile of microcystins reacting with protein phosphatase 1 was also obtained from the SELDI-TOF mass spectra.     

LC-MS/MS分析人参茎叶提取液中人参皂苷Rg1、Re降解产物

目的研究人参茎叶提取液中人参皂苷Rg1、Re加热后所产生的降解产物,并分析产物的结构。方法采用液相色谱/离子阱质谱联用仪对降解产物进行分析,并推测其结构,HPLC的条件为Agilent Extend-C18(250 mm×4.6 mm,5μm)色谱柱,流动相为乙腈-水,梯度洗脱70 min,检测波长203 nm,流速0.4 mL·min^-1,柱温30℃;质谱条件为正离子检测方式,毛细管电压3 000 V,喷雾器15 psi,干燥器流速12.0 L·min^-1,干燥器温度350℃,扫描范围100~1 000 m/z;碎裂器范围4 500~1 500 V。结果质谱图中有多种化合物,推测人参皂苷Rg1、Re在人参茎叶提取液的pH值环境下进行加热,会发生脱糖、脱羟基、环合等反应,生成多种降解产物。结论人参皂苷水溶液在人参茎叶提取液pH环境下加热的时间与温度对人参皂苷的降解非常敏感,说明此方法适用于人参皂苷类化合物的降解与分析。     

Analysis of potential anti-aging beverage Pru,a traditional Cuban refreshment,by desorption electrospray ionization-mass spectrometry and FTICR tandem mass spectrometry

Aging has been established as a major risk factor for prevalent diseases and hence, the development of anti-aging medicines is of great importance. Recently, herbal fermented beverages have emerged as a promising source of potential anti-aging drug. Pru, a traditional Cuban refreshment produced by decoction and fermentation of multispecies plants with sugar, has been consumed for many years and is claimed to have multiple medicinal properties. Besides the traditional method, Pru is also manufactured industrially. The present study analyzed the major components of both traditional Pru (TP) and industrial Pru (IP) to reveal their potential application in promoting the health span. We performed desorption electrospray ionization-mass spectrometry (DESI-MS) and acquired mass spectra by scanning over the 50–1200 m/z range in both positive and negative ion modes. Fourier transform ion cyclotron resonance (FTICR) tandem mass spectrometry (MS/MS) was performed for validating the compound assignments. Three important compounds were identified by comparing the MS and MS/MS spectra with reported literature and the online database. One of the identified compounds, gluconic acid, was found to be the most abundant shared metabolite between TP and IP whereas the other two compounds, magnoflorine and levan were exclusively detected in TP. The present study is the first report of component profiling in Cuban traditional and industrial Pru using DESI-MS and FTICR MS/MS, and reveals the potential application of Pru as a health-promoting agent.