小分子化合物在离子阱质谱中的分子离子反应研究

利用离子阱质谱的原理和特点，研究了小分子醇、醚、胺、醛、酮等有机化合 物（分子量小于200）在离子阱里的分子离子反应，总结了反应特点和规律，并把 它归类为自身化学电离（SCI）反应。以丁酮、丙烯醇为例，采用FTMS对反应产物 离子进行准确质量测定，验证了它们各自的分子离子反应结果。另外，把该类化合 物（30个）SCI反应的质谱图与NIST98库中的标准EI质谱图进行了比较，建立了 SCI质谱图库，提高了在离子阱质谱上对这类小分子化合物定性分析的准确率。     

气相色谱-质谱联用分析茶树油的成分

采用常规水蒸气蒸馏法从茶树枝叶中提取茶树油，经气相色谱-质谱联用分析，分离出47种成分，检索NI蚋8质谱数据库，与标准谱图对照鉴定了其中32种成分。应用Hewlett—Packard软件，按峰面积归一化法定量，所鉴定成分的馏出峰面积占总馏出峰面积的96．08％。     

色谱-串联质谱法测定天麻中53种禁用农药残留

建立超高效液相色谱-串联质谱联用（UPLC-MS/MS）及气相色谱-串联质谱联用（GC-MS/MS）法测定天麻中53种禁用农药残留。采用乙腈直接提取和基于QuEChERS原则的固相萃取法对样品进行处理。UPLC-MS/MS法采用电喷雾离子源，正离子模式下多反应监测，色谱峰面积外标法定量；GC-MS/MS法采用电子轰击离子源，色谱峰面积内标法定量。53种农药的质量浓度在一定范围内与响应值线性关系良好，相关系数均大于0.990，检出限为0.001～0.005 mg/kg，定量限为0.002～0.01 mg/kg。样品平均回收率为71.4%～118.2%，测定结果的相对标准偏差为1.4%～6.3%(n=6)。该方法能快速、有效地检测天麻中的禁用农药残留量，可用于天麻质量评价。     

同位素稀释质谱法测定高纯金属铟中的微量镉

采用同位素稀释高分辨电感耦合等离子体质谱法（ID—HR—ICPMS）对高纯金属铟中的微量镉进行定值方法研究。用^53Cr作为同位素稀释剂,通过对仪器测量参数以及样品制备和处理过程的优化研究,有效地克服了来自高含量金属基体、等离子体气体、试剂等产生的主要质谱干扰。与传统的光谱测量方法相比,无机质谱的测量方法提高了微量元素定值的准确度和测量精度。     

基质辅助激光解吸电离飞行时间质谱研究2: 四硫 富瓦烯化合物

采用基质辅助激光解吸电离飞行时间质谱(MALDI-TOF-MS),对四硫富瓦烯化合物进行质谱表征。在所用的实验条件下,样品很容易解吸电离生成单电荷分子离子,得到单同位素分辨的质谱图。26种实际样品的质谱分析结果表明;MALDI-TOF-MS可以比其它质谱方法更有效、更方便地用于此类化合物的质谱分析,解决了此类化合物不易进行质谱鉴定的难题。     

参芪降糖颗粒中微量元素与其疗效关系的研究

采用电感耦合等离子体质谱(ICP-MS)法，对参芪降糖颗粒中的二十种元素进行了分析，同时用塞曼测汞仪测定了样品中汞元素的含量。结果表明，参芪降糖颗粒对糖尿病的疗效与其中的微量元素有关。     

基质辅助激光解吸电离飞行时间质谱研究2: 四硫 富瓦烯化合物

采用基质辅助激光解吸电离飞行时间质谱(MALDI-TOF-MS),对四硫富瓦烯化合物进行质谱表征。在所用的实验条件下,样品很容易解吸电离生成单电荷分子离子,得到单同位素分辨的质谱图。26种实际样品的质谱分析结果表明;MALDI-TOF-MS可以比其它质谱方法更有效、更方便地用于此类化合物的质谱分析,解决了此类化合物不易进行质谱鉴定的难题。     

粒子束接口液相色谱－质谱应用

粒子束接口液相色谱－质谱应用黄峰（山东大学发酵工程国家实验室济南２５０１００）１前言化学和生物样品中的热不稳定性组分及难挥发性组分无法用气相色谱。质谱进行分析，因此液相色谱。质谱联用倍受关注。近二十年来发展了许多技术，如直接液体导入（ｄｉｒｅｃｔｌｉ...     

乳化汽轮机油分离水中的有机物组成分析

通过采用GDX树脂富集，气相色谱／质谱法定性分析，建立了乳化汽轮机油分离水中有机物分析程序．共检测出有机物成分28种，其中5种为汽轮机油的典型添加剂，表明水分对汽轮机油添加剂洗脱作用明显．     

大萼香茶菜挥发油化学成分的气相色谱/质谱法分析

采用常规水蒸气蒸馏法提取出大萼香香茶菜挥发油，经气相色谱－质谱联机分析，分离出116个峰，确认了其中60种成分，所鉴定的组分占总峰面积的75．77％。     

Determination of relative response factors of impurities in paclitaxel with high performance liquid chromatography equipped with ultraviolet and charged aerosol detectors

A case study was conducted to determine the relative response factors (RRFs) of paclitaxel-related impurities by high performance liquid chromatography (HPLC) equipped with an ultraviolet (UV) detector and charged aerosol detector (CAD) in tandem. The peak response using CAD was independent of analyte structure in an isocratic analysis for this application. After a sample containing known and unknown impurities was analyzed with HPLC-UV-CAD, an empirical approach was developed to calculate the RRFs for all impurities. The RRFs of known impurities were also determined by linear calibration curves. For known impurities, the RRFs values determined with two approaches are comparable. The new approach is effective yet simpler to determine the RRFs for unknown impurities or degradation products since the need for obtaining authentic pure materials was eliminated.     

米格列奈及其3个异构体杂质的反相液相色谱分离及质谱碎裂分析

建立了超高效反相液相色谱-高分辨质谱方法以实现米格列奈及其3种异构体杂质的分离，以ACQUITY UPLC HSS T3（100 mm×2.1 mm，1.8 μ m）为色谱柱，以水-乙腈-正戊醇（75：25：1）（用甲酸调节pH至1.8）为流动相，流速为0.4 mL/min。根据Q Exactive四极杆/静电场轨道阱高分辨质谱的精确质量数及碎裂情况，发现了米格列奈及3种异构体存在碎片离子丰度的明显差异，确认其中两种为本次新发现的异构体杂质，并推断了米格列奈及3种异构体杂质可能的质谱裂解机理。经验证，该方法的灵敏度、重复性及线性均满足分析要求。在此基础上，对米格列奈异构体杂质的来源进行了探讨，发现异构体杂质1可在高温下降解产生，并对各企业的米格列奈钙原料样品进行了测定。     

Synthesis,characterization and control of eight process-related and two genotoxic fingolimod impurities by a validated RP-UPLC method

An HPLC method has been described in the European Pharmacopoeia and United States Pharmacopeia for the determination of nine organic impurities (imp A–I) in fingolimod hydrochloride, a synthetic sphingosine-1-phosphate receptor modulator. The manufacturing process of fingolimod hydrochloride consists of multistep chemical synthesis wherein controls of precursors, intermediates and process steps should be performed to assure the final quality of the drug substance. We synthesized and isolated eight process-related impurities (FINI imp A–H) of fingolimod, which were different from the pharmacopoeial impurities. One unknown process-related impurity was found as a key intermediate (FINI) and was identified by LC–MS. Characterization of all of the impurities were done using spectroscopic techniques (¹H and ¹³C NMR, FTIR, MS), and the mechanistic pathways to the formation of these impurities were also discussed. Two of these impurities were evaluated as potential genotoxic impurities owing to their alerting structures and alkylating properties (alkyl sulfonates and alkyl halides, class 3, ICH M7). We also developed and validated an RP-UPLC method in line with ICH Q2 guidelines for control these impurities (FINI imp A–H) and to assure the pharmacopoeial quality drug substance.     

Comparative evaluation of organic contamination sources from roller and pencil type PVA brushes during the Post-CMP cleaning process

In post-CMP (chemical mechanical polishing) processing, the use of poly vinyl acetal (PVA) brushes to clean the wafer surface is one of the most effective and prominent techniques applied for the removal of CMP contaminants. Recently, organic contaminants induced in different types of PVA brushes during brush manufacturing have been drawing substantial research interest in CMP communities. In this study, investigated the root cause of these residual organic impurities in two different types of PVA brushes was investigated: roller and pencil type brushes. PVA roller brushes have a skin layer due to the brush molding process, but pencil-type PVA brushes do not have the skin layer. Extraction of organic impurities from both types of brushes was accomplished using an ultrasound-assisted technique at a sonication frequency of 40 kHz, and input power of 600 W. Further evaluation of these organic impurities using Field Emission Scanning Electron Microscopy (FE-SEM) revealed a large number of organic impurities in roller brushes and negligible impurities in pencil brushes. Time of flight secondary ion mass spectrometry (TOF-SIMS) analysis confirmed polydimethylsiloxane (PDMS) as the organic impurities extracted from PVA roller brushes, which were generated during the brush manufacturing process. The PDMS content in PVA roller brushes was further analyzed using FE-SEM micrographs via dissolving the organic impurities in tetramethylammonium hydroxide solution (TMAH). During brush fabrication, the high content of PDMS organic impurities in roller PVA brushes is essentially attributed to the presence of the additional skin layer formed by the mold releasing agent at the mold-cavity interface.     

Development and optimization of an HPLC analysis of citalopram and its four nonchiral impurities using experimental design methodology

In this study, the RP-HPLC method was investigated for the separation of citalopram and its four impurities by use of statistical experimental design. Initially, the influence of different experimental conditions (buffer pH, flow rate, and column temperature) on the chromatographic behavior of citalopram and its four impurities was investigated by use of partial least squares regression (PLSR) and multilayer perceptron (MLP) artificial neural networks (ANNs) trained by back-propagation. The developed models and the corresponding response surface plots were used to select the optimal HPLC conditions, buffer pH 7.0, flow rate 1.0 mL/ min, and column temperature 25 degrees C, for an efficient separation of citalopram and its four impurities. The elaborated HPLC method was found to be linear, specific, sensitive, precise, accurate, and robust. Retention times of citalopram and its impurities, obtained with the developed HPLC method, and the computed molecular parameters of the examined compounds were used in a quantitative structure retention relationship (QSRR) study. The PLSR and ANN algorithms were applied for the development of the QSRR methods. The MLP-two layers-ANN-QSRR model with root mean square error of prediction 0.105 and r(2) (observed versus predicted) 0.978 was selected. Since many different reaction conditions are applied for the synthesis of citalopram, different impurities and degradation products can be formed. Therefore, the developed QSRR model can be extended to the prediction of the retention times with the other citalopram impurities, degradation products, and metabolites.     

Application of LC–NMR to the identification of bulk drug impurities in NK1 antagonist GW597599 (vestipitant)

Liquid chromatography‐NMR (LC–NMR) spectroscopy was used to obtain detailed information regarding the structure of the major bulk drug impurities present in GW597599 (vestipitant). The one‐dimensional ¹H LC–NMR experiments were performed in both continuous and stop‐flow modes on a sample of GW597599 (vestipitant) enriched with mother liquor impurities. The information derived from both LC–NMR and LC–MS data provided the structural information of all major impurities. The full characterisation of the impurities by high‐resolution NMR spectroscopy was ultimately performed on appropriately synthesised compounds. Copyright © 2010 John Wiley & Sons, Ltd.     

高效液相色谱法测定硫酸伏拉帕沙原料药中杂质

建立了高效液相色谱法测定硫酸伏拉帕沙原料药中杂质的方法。采用ACE Excel C18(4.6 mm×250 mm,5μm)色谱柱;以pH 2.5的H3PO4溶液为流动相A,乙腈为流动相B,梯度洗脱;检测波长为260 nm;进样量为20μL。结果表明,主成分与各杂质的分离度良好,各已知杂质在测定的范围内具有良好的线性(r>0.9996)。方法可用于硫酸伏拉帕沙原料药的质量控制。     

气相色谱法检测工业用乙二醇纯度及杂质

以Rtx-624色谱柱（30 m×0.32 mm×1.8 μm）为分析柱进行分析，采用校正面积归一化法，建立了检测工业用乙二醇纯度及其中有机杂质的气相色谱分析法。该法可检测传统乙烯法制得的乙二醇中固有杂质二乙二醇、三乙二醇和1，3-二氧杂烷-2-甲醇，同时也适用于检测草酸酯加氢法制得的乙二醇中的新杂质（1，2-丁二醇、1，4-丁二醇、1，2-己二醇、碳酸乙烯酯等）。结果表明，该法具有良好的重复性和较高的检测灵敏度，检出限最低可达0.0002%（质量分数），回收率在91.2%~105.4%之间。该法在乙二醇生产控制、产品检测、市场贸易等过程中具有良好的应用前景。     

Reversed-phase ultra-performance liquid chromatographic method development and validation for determination of impurities related to torsemide tablets

A simple RP-ultra-performance LC method was developed and validated for determination of impurities related to torsemide tablets. The rapid method provided adequate separation of all known related impurities and degradation products. Separation was achieved on a Zorbax SB-C18 column (50 x 4.6 mm id, 1.8 microm particle size) with binary gradient elution, and detection was performed at 288 nm. The drug product was subjected to oxidative, hydrolytic, photolytic, and thermal stress conditions to prove the specificity of the proposed method. The linearity and recovery were investigated for known impurities in the range of 0.025 to 1.0%, with respect to the drug concentration in the prepared sample. The linearity of the calibration curve for each of the impurities and torsemide was found to be very good (r2 > 0.999). Relative response factors for each of the known impurities were established by the slope ratio method from the linearity study.     

Separation,Characterization, and Quantification of Atorvastatin and Related Impurities by Liquid Chromatography-Electrospray Ionization Mass Spectrometry

A method coupling high-performance liquid chromatography with diode-array detector and electrospray ionization mass spectrometry (HPLC-DAD-ESI/MSⁿ) has been developed for the separation and characterization of atorvastatin and its related impurities. The results obtained using positive ion mode showed some diagnostic fragments that are useful for the identification of atorvastatin related impurities in real samples. Quantitative analysis of drug impurities was performed in the multiple reaction monitoring mode. Quantification limits for impurities were in the ranges 21.5–70.8 ng mL^?1. The method was successfully applied to the drug purity evaluation and quantitative determination of atorvastatin related impurities in bulk drugs and pharmaceutical formulations.