5种吡咯烷酮衍生物的电喷雾离子阱质谱分析初探

目的探讨5种结构相似的吡咯烷酮衍生物的质谱裂解规律。方法在正离子检测方式下,用电喷雾离子阱质谱法对吡拉西坦、奥拉西坦、茴拉西坦、奈非西坦和左乙拉西坦进行多级质谱分析。结果各化合物在二级质谱分析时,均可发生酰胺键断裂,生成脱去含氮基团的碎片离子m／z126（吡拉西坦和奈非西坦）、m／z142（奥拉西坦）、m／z135（茴拉西坦）、m／z154（左乙拉西坦）;在三级质谱分析时,除茴拉西坦外,则进一步发生脱去羰基的反应,生成稳定的碎片离子m／z98、m／z114和m／z126。结论通过多级质谱分析可获得吡咯烷酮衍生物分子丰富的结构信息,并可用于该类化合物的快速结构解析和定量分析。     

8种氨基糖苷类抗生素的电喷雾离子阱质谱

目的探讨8种结构相似的氨基糖苷类抗生素的质谱裂解规律。方法在正离子检测方式下，用电喷雾离子阱质谱法对庆大霉素、小诺霉素、西索霉素、依替米星、奈替米星、威替米星、卡那霉素A和妥布霉素进行多级质谱分析。结果各化合物在二级质谱分析时，均可发生B环与C环之间的糖苷键断裂，生成脱去C环（氨基葡萄糖）的碎片离子m/z 322（庆大霉素、小诺霉素和西索霉素）、m/z 350（依替米星、奈替米星和威替米星）和m/z 324（卡那霉素和妥布霉素）；在三级质谱分析时，则进一步发生A环（氨基葡萄糖）与B环（脱氧链霉胺）之间的糖苷键断裂，生成A环或B环的碎片离子m/z 163和 m/z 191或m/z 160和m/z 162。 结论通过多级质谱分析可获得氨基糖苷类抗生素分子丰富的结构信息，并可用于该类化合物的快速结构解析和定量分析。     

MCR-ALS应用于7-乙基-10羟基喜树碱中喜树碱含量的测定

目的：应用多元曲线分辨-交替最小二乘（MCR-AIS）法，对7-乙基-10-羟基喜树碱与喜树碱的色谱重叠峰进行分辨，并对杂质喜树碱进行定量。方法：以渐进因子分析（EFA）解析结果作为初始值对喜树碱与7-乙基-10-羟基喜树碱的色谱重叠峰进行ALS迭代优化，直至收敛。结果：采用此方法分辨所得光谱还原率高，定量结果的浓度值与真实值之间线性关系良好。结论：本方法用于药物色谱重叠峰分辨结果可靠。     

7-乙基-10-羟基喜树碱的合成

用喜树碱乙基化制得的7-乙基喜树碱在冰乙酸中用双氧水氧化成N-氧化物,再经光照重排制得7-乙基-10-羟基喜树碱,并优化了反应条件,总收率49%.     

10-羟基喜树碱衍生物的合成及体外抑制肿瘤活性

目的寻找高效低毒的喜树碱类抗肿瘤新药。方法合成7个喜树碱衍生物（3~9），经¹HNMR，IR，MS分析确证了所合成化合物的结构，经MTT法筛选了对宫颈癌Hela、肝癌BEL-7402、胃癌7901和大肠癌CCL-187瘤株的体外抑制肿瘤活性。结果7个化合物分别对前三种瘤株有效，其中化合物4对前三种瘤株均有较好的体外抑制肿瘤细胞活性，尤其对宫颈癌Hela细胞的抑制活性大于10-羟基喜树碱。结论该类化合物的抗癌活性值得进一步研究。     

高效液相-电喷雾质谱分析7-羟基黄酮在大鼠体内的代谢产物

目的:研究7-羟基黄酮在大鼠体内的代谢。方法:应用高效液相-电喷雾质谱检测大鼠灌胃7-羟基黄酮后血浆、尿液、胆汁和粪便中的代谢产物。实验采用Zorbax C18色谱柱,二元线性梯度洗脱进行色谱分离,并与电喷雾质谱联用,根据负离子模式的分子离子峰获得化合物相对分子质量信息,推测化合物的可能结构。结果:在大鼠尿液、粪便、血浆、胆汁中检测到原形成分7-羟基黄酮和7-羟基黄酮葡萄糖醛酸结合物,在胆汁或尿中尚检测到7-羟基黄酮硫酸结合物。结论:7-羟基黄酮在大鼠体内主要以Ⅱ相代谢产物葡萄糖醛酸结合物和硫酸结合物的形式存在。     

基于电喷雾静电场轨道阱质谱的24个邻苯二甲酸酯碎片离子解析

目的:基于相容性研究中未知提取物和浸出物的结构鉴定需求,利用电喷雾静电场轨道阱质谱的分辨率优势,对24个邻苯二甲酸酯类化合物质谱信息进行采集,并对各碎片离子的结构形态及裂解途径进行解析。方法:采用超高效液相色谱-四极杆/静电场轨道阱质谱法进行定性测定。色谱柱为Agilent Proshell 120EC-C₁₈色谱柱(100 mm×4.6 mm, 2.7μm);流动相A为0.1%乙酸水溶液,流动相B为甲醇,流动相C为乙腈;梯度洗脱。ESI正电离模式;喷雾电压3 500 V;鞘气流速7 L·min^-1,辅助气流速12 L·min^-1;离子传输管温度325℃;离子源温度320℃;采用一级全扫描和二级子离子扫描的数据采集模式。设置扫描分辨率120 000,全质量扫描范围m/z 50～1 000。结果:24个邻苯二甲酸酯类化合物一级质谱响应良好,[M+H]⁺离子显著可见;二级碎片离子在高、中、低质荷比分布均匀,显示有强的m/z 149的特征峰,并不同程度伴生m/z 167、121、111、93等特征离子。在...     

10-羟基喜树碱的合成

喜树碱经H2O2氧化所制得的喜树碱N-氧化物,于酸性条件下经紫外线照射在10-位引入羟基,最后经柱色谱分离纯化得到纯度98%以上的目标化合物,收率33%.     

7-乙基-10-羟基喜树碱脂质体在大鼠体内的代谢和排泄

目的考察7-乙基-10-羟基喜树碱(SN-38)脂质体经静脉注射后,在大鼠尿液、粪便中的代谢产物以及以SN-38原形药物排泄的量。方法大鼠尾静脉单次给予2.77 mg/kg SN-38脂质体,分别于0～6、6～12、12～24、24～48 h分段收集尿液、粪便,采用UPLC/Q-TOFMS法对SN-38脂质体在大鼠尿液、粪便中的代谢产物进行鉴定,并且建立HPLC法,用于大鼠尿液及粪便样品中SN-38原形药物的排泄量的测定。结果 SN-38脂质体的在大鼠体内的代谢产物经鉴定为SN-38G。48 h内脂质体组共有1.57%的原形药物经过尿液排出,共有12.94%的SN-38原形药物经过粪便排出。结论 SN-38脂质体只有少部分以原形药物经尿液和粪便排出体外。     

庆大霉素的电喷雾质谱分析

目的应用电喷雾离子化串联质谱探讨庆大霉素的质谱断裂规律。方法在正离子检测模式下,以电喷雾离子化法对庆大霉素进行多级质谱分析。结果在二级质谱分析中,庆大霉素中的各化合物均发生B环和C环间的糖苷键断裂,生成脱去C环（氨基葡萄糖）的二级碎片离子m/z322.0,再对m/z322.0进行分析时,生成分别脱A环（氨基葡萄糖）或B环（脱氧链霉胺）的碎片离子m/z163.0或m/z160.0。结论通过对庆大霉素的电喷雾质谱的分析,丰富了其分子结构信息,并可用于该类化合物的结构快速鉴定和定量分析。     

传统中药川乌炮制前后的离子阱质谱研究

目的：通过应用电喷雾－离子阱质谱,研究了炮制前后的川乌药材成分,以揭示川乌炮制减毒的原理。方法：对3种乌头对照品进行了离子阱多级质谱分析,归纳其裂解规律。对炮制前后的川乌药材进行液－质联用分析,并对各色谱峰进行归属。结果：通过对比炮制前后的质谱总离子流图及紫外色谱图,提出了川乌炮制减毒的两方面原因。结论：同时指出了将液－质联用技术引入中药炮制品的质量控制是十分必要的。     

Identification of metabolites of crude and processed Fructus Corni in rats by microdialysis sampling coupled with electrospray ionization linear quadrupole ion trap mass spectrometry

A microdialysis (MD) sampling coupled with electrospray ionization linear quadrupole ion trap mass spectrometry (LTQ-MSⁿ) method has been developed for rapid and sensitive analysis of rat microdialysate metabolite profile of Fructus Corni, a well-known Traditional Chinese Medicine (TCM). The purified samples were separated by a reversed-phase HPLC with C₁₈ column under a gradient elution. Parent compounds and metabolites of crude and processed Fructus Corni of Jiu Zheng Pin (JZP, JZP is produced after steaming the crude drug pre-steeped in wine) were detected by the on-line MSⁿ detector in negative scan model. The identification of the metabolites and their structural elucidation were performed by comparing the changes in molecular mass and defining sites of biotransformation based on the accurate MSⁿ spectral information of diagnostic fragment ions. In this work, we used such strategies for the identification of the parent compounds and metabolites of crude and processed Fructus Corni in rats, and seven parent compounds and three new metabolites of Fructus Corni were found in rats for the first time. This study provides important structural information regarding to the metabolism of crude Fructus Corni and its JZP. Furthermore, this work also demonstrated the possibilities of using microdialysis sampling coupled with LC-MSⁿ approach for identification of bioactive compounds from TCM in vivo.     

电喷雾离子阱质谱法研究蛋白与小分子配体间非共价结合的方法学探讨

以小檗碱与α₁-酸性糖蛋白间的非共价结合作用为例，提出了一种新的质谱滴定法。其主要假定条件是：当蛋白与小分子配体间有一定亲合力、且作用配体的摩尔量大于作用蛋白的摩尔量时，蛋白复合物总浓度与作用蛋白总浓度近似相等。通过不同摩尔量比的小檗碱对α₁-酸性糖蛋白的电喷雾离子阱质谱(ESI-IT/MS)滴定实验，分析小檗碱与α₁-酸性糖蛋白复合物的结合特点，并应用荧光法进行验证。结果表明应用质谱滴定法与荧光法得到的小檗碱与α₁-酸性糖蛋白复合物的结合特性常数(如稳定常数、结合位点数、作用力类型)基本相同。与传统质谱滴定法相比，本文提出的ESI-IT/MS滴定法用于蛋白与小分子配体间非共价结合特性研究，所用仪器相对便宜，方法简单且适应强，在一些研究体系中可得到更准确的实验结果。     

生长抑素一级结构的电喷雾质谱分析

目的生长抑素的分子量及其一级结构的测定。方法应用电喷雾质谱法(ESI-MS)测定了环肽药物生长抑素的分子量,用2-巯基乙醇将生长抑素的双硫键还原,再用源内碰撞诱导解离技术进行测定,根据其典型碎片离子确证其氨基酸序列。结果测得生长抑素准分子离子峰［M+H］⁺ m/z 1 637.8, ［M+Na］⁺ m/z 1 659.5及［M+2Na-H］⁺ m/z 1 681.5,［M+2H］²⁺ m/z 819.5及［M+H+Na］²⁺ m/z 830.3,表明生长抑素的分子量为1 636.7,与理论值一致。将双硫键还原后,用CID技术进行测定,得到了一系列y和b系列的特征碎片离子,证实生长抑素还原产物的氨基酸序列为A-G-C-K-N-F-F-W-K-T-F-T-S-C。结论用ESI-MS法测得的生长抑素的分子量及一级结构与理论值相符。     

Identification of degradation products of diclofenac by electrospray ion trap mass spectrometry

The degradation products of diclofenac in aqueous dosage form in accelerated storage conditions were characterized by electrospray ionization-ion trap mass spectrometry (ESI-MS). Liquid chromatography (LC)-MS analyses revealed the presence of three degradation products. ESI-MS(n) spectra were used to study diclofenac fragmentation in detail and to characterize the structures of degradation products. A previously described degradation product, formed by a cyclization reaction of diclofenac producing the indolinone derivative, was found. As any hydroxylated product was found, no oxidation seems to occur in the dosage form used. On the contrary, two degradates have been detected and identified, leading to a primary alcohol structure or an aldehyde function in place of the acetate group of diclofenac.     

Peptide profiling of Internet‐obtained Cerebrolysin using high performance liquid chromatography – electrospray ionization ion trap and ultra high performance liquid chromatography – ion mobility – quadrupole time of flight mass spectrometry

Cerebrolysin, a parenteral peptide preparation produced by controlled digestion of porcine brain proteins, is an approved nootropic medicine in some countries. However, it is also easily and globally available on the Internet. Nevertheless, until now, its exact chemical composition was unknown. Using high performance liquid chromatography (HPLC) coupled to ion trap and ultra high performance liquid chromatography (UHPLC) coupled to quadrupole‐ion mobility‐time‐of‐flight mass spectrometry (Q‐IM‐TOF MS), combined with UniProt pig protein database search and PEAKS de novo sequencing, we identified 638 unique peptides in an Internet‐obtained Cerebrolysin sample. The main components in this sample originate from tubulin alpha‐ and beta‐chain, actin, and myelin basic protein. No fragments of known neurotrophic factors like glial cell‐derived neurotrophic factor (GDNF), neurotrophin nerve growth factor (NGF), brain‐derived neurotrophic factor (BDNF), and ciliary neurotrophic factor (CNTF) were found, suggesting that the activities reported in the literature are likely the result of new, hitherto unknown cryptic peptides with nootropic properties. Copyright © 2015 John Wiley & Sons, Ltd.     

Metabolism of SFZ—47 in chicken embryo by liquid chroma—tography—electrospray ion trap mass spectrometry

AIM:To develop an alternative method for investigation of drug metabolism by fertilized chicken eggs using 3H-1,2-dihydro-2-(4-methyl-phenylamino) methyl-1-pyrrolizinone (SFZ-47) as a probe drug. METHODS:SFZ-47(15 mg) was injected into the albumen of eggs from standardized breed chickens previously incubated for 10d. After 72 h of further incubation, the allantoic liquid was subjected to solid phase extraction on XAD-2 columns and analyzed by liquid chromatography-electrospray ion trap mass spectrometry method. RESULTS: Three major metabolites were identified, namely 4-(3H-1,2-dihydro-1-pyrrolizinone-2-methyl-amino) benzyl alcohol (SFZ-47-OH), 4-(3H-1,2-dihydro-1-pyrrolizinone-2-methyl-amino)-benzoic acid (SFZ-47-COOH), and its glucuronide conjugates. The metabolic profile was little different from that previously found in rabbits and dogs. CONCLUSION: The result demonstrates the usefulness of the fertilized chicken egg as a convenient source of both phase I and phase Ⅱ metabolites for further metabolism studies of SFZ-47.     

电喷雾离子化质谱分析环孢菌素的组成氨基酸

应用电喷雾离子化质谱对9个环孢菌素类化合物强酸水解后的产物进行分析,获得环孢菌素类化合物一些组成氨基酸的特征分子离子峰,特别是1位上特殊的氨基酸-MeBmt,实验结果表明本方法在测定环孢菌素中的MeBmt和其它组成氨基酸方面具有进样量少、快速、准确,无需对照品等优点,可用于环孢菌素类化合物的初步快速鉴别。