色谱-质谱法分析立他司特中强制破坏后的降解产物

目的探索方法对立他司特(lifitegrast,LTST)强制降解后的产物进行色谱分离,采用LC-MS对其结构鉴定。方法色谱柱YMC Triart C_(18)(4.6×250 mm,5μm);流动相乙腈-0.1%磷酸水溶液(梯度洗脱),流速1.0 mL·min^(-1);紫外检测波长220 nm。同时采用UPLC串联6540B Q-TOF对主要的降解产物进行初步定性研究。结果所开发的方法,可使立他司特各杂质有效分离,并初步鉴定出7个主要的降解产物结构。结论本法可用于立他司特的有关物质检测,对其药品质量的控制提供了较为重要的参考依据。

牛奶中四环素类药物残留的确证方法——液质联用法

为了确证牛奶中土霉素、四环素、金霉素的残留,建立了电喷雾高效液相色谱/串联质谱法,采用正离子检测,选择离子方式扫描.牛奶样品经McIlvame-EDTA缓冲溶液提取离心后,上清液过C18小柱净化后甲醇洗脱,然后氮气吹干,甲醇-水(30:70)溶解(以去甲金霉素为内标)后进行分析.结果表明,牛奶中土霉素、四环素和金霉素的检测限(LODs)为0.01 mg/L,定量限(LOQs)为0.025 mg/L.3种药物在0.05～0.5 mg/L范围内均呈良好线性关系,并且3个添加浓度的平均回收率范围为70.0%～87.6%,批内变异系数不大于10%,以最大残留限量浓度添加后所测得回收率的批间变异系数小于15%.本方法特异性强、灵敏度高、准确可靠,可作为牛奶及其他动物组织中四环素类药物残留的确证方法.

大豆异黄酮的去酰基化结合液质联用系统提高总异黄酮含量测定准确性的研究

为了准确测定原料和产品中的总大豆异黄酮含量,建立了通过碱水解法将不稳定形式的大豆异黄酮(含丙二酰基和乙酰基)转化为稳定形式(含葡萄糖苷和苷元)的液相色谱-三重串联四极杆液质联用仪(liquid chromatography-triple tandem quadrupole liquid mass spectrometer,LC-MS/MS)测定方法,并进行了验证。去酰基化后总大豆异黄酮由大豆苷、黄豆苷、染料木苷、大豆苷元、黄豆苷元、染料木素这六种化合物组成。它们的线性范围分别为0.1~4.1μg/mL、0.11~4.36μg/mL、0.12~4.84μg/mL、0.1~4μg/mL、0.11~4.58μg/mL、0.11~4.37μg/mL。大豆异黄酮原料和产品药片的相对标准偏差(RSD)分别为4%和2%,原料和片剂中各成分的回收率均在90%~110%之间,且所有组分分析完成时间不超过10分钟。大豆异黄酮量的准确测定保证了大豆异黄酮类原料中规定的异黄酮量,以及产品标签上的正确异黄酮量。

高分辨质谱法快速测定芬太尼类物质及其质谱裂解规律

目的 采用UPLC-Q Exactive高分辨质谱法,对25种芬太尼类物质及2种前体化合物建立了定性定量检测方法。依据高分辨质谱(HRMS)提供的精确质量数及特征离子碎片,分析质谱裂解规律,实现无标准品的情况下对芬太尼类疑似物进行结构鉴定,解决新精神活性物质监管滞后的问题。方法 固体疑似物经甲醇超声提取后测定;液体疑似物采用乙腈进行液-液萃取,盐析分层,取乙腈层测定。采用Hypersil GOLD C18(150mm×2.1mm×1.8μm)色谱柱,以甲醇-2mmol/L乙酸铵含0.1%甲酸水溶液为流动相进行梯度洗脱;质谱采用正离子模式、全扫描及目标离子二级扫描(Full MS/dd-MS;)进行碎片信息的采集,以建立27种化合物的二级质谱谱库用于定性分析。结果 27种化合物包括同分异构体均实现了有效分离,检测限为0.05~2ng/m L,固体基质的定量限为0.5μg/kg,液体样品定量限为0.5ng/m L,加标回收率为77.03%~115.07%。在ESI模式下,芬太尼类物质的主要裂解途径:1)哌啶环上的γ-H重排到羰基氧上,发生麦氏重排(Mc Lafferty rearrangement,Mc L),羰基的β-键开裂,形成m/z 188的基峰;2)哌啶环内氢转移形成双键,激发逆Diels-Alder(RDA反应)哌啶环内裂解,形成m/z 160、146、134、132等特征离子;3)哌啶环与苯乙基部分发生N-C裂解,形成m/z 84、105的碎片离子。结论 本研究有助于已知母核的芬太尼类新精神活性物质化学结构的鉴定,可用于执法查获物中的芬太尼类物质的定性鉴别和定量检测。

Pharmacokinetics of nifedipine sustained-release tablets in healthy Chinese volunteers

Aim To establish a LC-MS method for determining the concentration of nifedipine in human plasma and to evaluate the pharmacokinetic characteristics of nifedipine sustained-release tablets. Methods A XB-C18 （5 μm, 4.6 mm ×150 mm） column and a mobile phase of methanol： 0.01 mol·L^-1ammonium acetate （60：40, V/V） were used to separate nifedipine, the detections was accuracy under atmosperic pressure electronic spray ionization （AP-ESI） mode and ion mass spectrum （m/z） of 314.9 [M＋H]^＋ for nifedipine, and 320.8 [M＋H]^＋ for lorazepam （Internal Standard, IS）. Results The linear range of nifedipine was 0.3 - 80 ng·mL^-1 （ r = 0.9997）, and the limit of quantitation （LOQ） was 0.3 ng·mL^-1. The nifedipine pharmacokinetic parameters after a single dose of 20 mg nifedipine sustained-release tablets test （T） or reference （R） were as the followings, t1/2 （6.73 ± 2.00） h and （7.04 ± 2.18） h, Tmax （4.28 ± 0.70） h and （4.48 ± 0.70） h, Cmax（39.66 ± 10.58） ng·mL^-1 and （40.19 ± 10.97） ng·mL^-1, AUC0-36 （391.63 ± 108.55） ng·mL^-1·h and （387.57 ± 121.51） ng·mL^-1·h, and AUC0-∞ （408.28 ± 121.16） ng·mL^-1·h and （406.15 ± 133.13） ng·mL^-1·h. The relative bioavailability of nifedipine sustained-release tablets （test） was （103.02 ± 13.93） %. Conclusion LC-MS method for the determination of concentrations of nifedipine in human plasma was sensitive and accurate, and could be used in nifedipine bioavailability and pharmacokinetic studies.

Conversion of Cellulose to 5-Hydroxymethylfurfural in Water- Tetrahydrofuran and Byproducts Identification

Conversion of cellulose into platform chemical 5-hydroxymethylfurfural （HMF） in water-tetrahydrofuran （THF） co-solvents under acidic condition was studied. 38.6% of HMF was obtained with low cellulose concentration of 2.4wt%, but levulinic acid （LA） and solid humins became the main products with high cellulose concentration. The soluble byproducts were analyzed by high performance liquid chromatography/multiple stage tandem mass spec-trometry, and chemicals with formula of C9H16O4、 C10H14O4、 C11H12O4、C12H10O5 and C12H16O8 were detected. THF could participate in the reaction via ring-opening into 1,4-butanediol followed by esterification with LA into C9H16O4 or etherification with HMF into C10H14O4. C11H12O4 was formed by esterification of HMF with LA, C12H10O5 was formed by self-etherification of HMF, while C12H16O8 was formed by acetalization of HMF with glucose. Self-etherification of HMF and etherification of HMF with 1,4-butanediol were identified as two main side reactions.

Determination of penehyclidine hydrochloride in beagle dog plasma by liquid chromatography-electrospray ionization mass spectrometry and the pharmacokinetic study

To develop a fast and sensitive liquid chromatography-mass spectrometry method for the determination of penehyclidine hydrochloride （PH） in beagle dog plasma. PH and diphenhydramine hydrochloride （internal standard, IS） were extracted with a solvent mixture of petroleum ether-ethyl ether （7：3）. Chromatographic separation was achieved on a reversed-phase Eclipse XDB-C18 column （4.6 mm × 150 mm, 5 um） using the eluent of methanol-water （5 mmol/L ammonium acetate） （90：10, v/v, pH 5.8） as mobile phase. The electrospray ionization source was set at the positive multiple reaction monitoring （MRM） mode. This method involved the use of the [M＋H]^＋ ions of PH and diphenhydramine hydrochloride at m/z 316.4- 128.2 and m/z 256.4-167.2. The calibration curve was linear in the range of 1-1000 ng/mL with a correlation coefficient of 0.9988. The lower limit of quantification was 0.05 ng/mL. The precision, accuracy and recovery of the method were acceptable. Following intravenous injection admires＇ tration at doses of 0.5, 1 and 5 mg/kg PH, the main pharmacokinetic parameters were as the followings, t1/2a 0.33 h, t1/2β 2.44 1% tmax 0.058 1% AUC and Cmax exhibited a linear increase along with the increase of dose. The two-compartment model fit the three dose groups. This method was sensitive, accurate and fast for the determination of concentration of PH in beagle dog plasma. It could be used in pharmacokinetic studies of PH.

Reaction Kinetics of Trans-Sobrerol and 8-p-Menthen-1,2-diol with Hydroxyl Radical in Aqueous Solution： A Combined Experimental and Theoretical Study

Trans-sobrerol （Sob） and 8-p-menthen-1,2-diol （Limo-diol） are the primary products in the atmospheric oxidation of α-pinene and limonene, respectively. Because of their low volatility, they associate more likely to the liquid particles in the atmosphere, where they are subject to the aqueous phase oxidation by the atmospheric oxidants. In this work, through experimental and theoretical study, we first provide the rate constants of Sob and Limo-diol reacting with hydroxyl radical （.OH） in aqueous solution at room temperature of 3044-3 K and 1 atm pressure, which are （3.05±0.5）×10 9 and （4.57±0.2）×10 9 L/（mol.s）, respectively. Quantum chemistry calculations have also been employed to demonstrate the solvent effect on the rate constants in aqueous phase and the calculated results agree well with the measurements. Some reaction products have been identified based on liquid chromatography combined with mass spectroscopy and theoretical calculations.

不同采收期大花罗布麻叶中黄酮类成分含量的测定

建立大花罗布麻叶中黄酮类成分槲皮素、芦丁、金丝桃苷的高效液相色谱-串联质谱（HPLC-MS/MS）测定方法,分析不同采收期的大花罗布麻叶中这3种黄酮类成分的变化.结果表明,芦丁在大花罗布麻叶的整个生长期中均未检出;槲皮素在10月份有检出,其他月份无检出;金丝桃苷整个生长期中均有检出,其中6～8月含量较高,故适宜采收期为6～8月;该检测方法加标回收率为98.0％～102.3％,相对标准偏差（RSD）为1.44％～2.63％,在各自的浓度范围内线性关系良好.高效液相色谱-串联质谱法可用于大花罗布麻叶中3种黄酮类成分的含量测定.

苯醚甲环唑在番茄和土壤中的残留动态研究

采用田间试验方法研究苯醚甲环唑在番茄和土壤中的残留与降解动态,应用超高效液相色谱-串联四级杆液质联用法（UPLC-MS/MS）进行定性和定量分析.结果表明,苯醚甲环唑在番茄中的平均回收率为90.3%-107.1%,变异系数为0.7%-7.8%;在土壤中的平均回收率为80.1%-104.7%,变异系数为7.2%-9.1%.动态研究结果表明：苯醚甲环唑在番茄中的降解比在土壤中快,在山东和河南两地番茄中的降解半衰期分别为3.3-3.8和3.3 d;在土壤中的降解半衰期分别为19.9-22.4和13.1-18.8 d.10%苯醚甲环唑微乳剂在番茄上按照推荐剂量最多施药2次,采收期距最后一次施药3 d,番茄中苯醚甲环唑残留量小于0.158 mg/kg.低于日本和澳大利亚规定的最高残留限量（MRL,0.5 mg/kg）,说明苯醚甲环唑为低残留、易降解农药.

丙环唑在香蕉和土壤中的消解动态及残留安全性评价

采用田间试验方法研究丙环唑在香蕉和土壤中的残留动态。超高效液相色谱-串联四极杆液质联用法进行(UPLC-MS/MS)定量定性分析。丙环唑在香蕉中的平均回收率为81.9%～100.2%;在香蕉全果中的平均回收率为72.8%～103.6%;在土壤中的平均回收率为81.9%～94.6%。动态结果表明:丙环唑在香蕉全果中比在土壤中消解快,其消解半衰期分在香蕉全果和土壤中分别为13.9d和23.3d。在香蕉上按照推荐剂量最多施药2次,采收期距最后一次施药40d,香蕉果肉中丙环唑残留量小于0.011mg/kg。低于中国规定的最高残留限量(MRL,0.1mg/kg),说明该药为低残留、易消解农药。

新疆紫草及其毛状根中萘醌类化合物的研究

目的 运用高效液相色谱-电喷雾离子阱液质联用技术（HPLC-ESI-MS/MS）鉴别新疆紫草中的萘醌类化合物,比较分析了9个样品中（新疆紫草原植物根及毛状根）萘醌类成分种类和含量的差异。方法 采用BDS C18色谱柱,以0.1%甲酸（A）-甲醇（B）梯度洗脱,使用ESI离子源,流速1.0 m L·min-1,质量扫描范围（m/z）150∽400,负离子模式下采集数据。结果 新疆紫草中含有紫草素、β-羟基异戊酰紫草素、乙酰紫草素、去氧紫草素、异丁酰紫草素、β,β-二甲基丙烯酰紫草素、异戊酰紫草素或α-甲基-正丁酰紫草素7种萘醌类化合物;但其毛状根中不含紫草素成分,其他成分与新疆紫草相同。紫草素及其衍生物的种类及含量因不同区域、不同毛状根而有所差异。此外,硝酸银（Ag NO3）及营养成分能够增加毛状根中紫草素及其衍生物的种类且影响各成分的含量。结论 萘醌类化合物的种类及含量受环境及培养条件的影响而变化。该方法可为新疆紫草及其毛状根的药效物质基础研究及其开发利用提供科学依据。

面膜中荧光增白剂的透皮吸收特性及对皮肤刺激性的实验研究

为了研究含脂溶性荧光增白剂(FWAs)面膜的透皮吸收特性及其对皮肤刺激性,采用改良的Franz透皮扩散池,以离体雄性大鼠腹部皮肤为模型,通过高效液相色谱-三重四极杆液质联用法测定接收液中5种吡唑啉型荧光增白剂的含量,计算其不同透皮时间段的累计渗透量,并对试验终期皮肤中FWAs的贮留量进行检测;按《化妆品安全技术规范》(2015年版)中皮肤刺激性实验要求,采用家兔进行皮肤刺激性试验。结果显示,5种脂溶性FWAs呈现良好的线性关系,相关系数(r;)均大于0.999,检出限为0.5~10.0 pg,定量限为2.0~30.0 pg,平均回收率和相对标准偏差分别为95.2%~102.1%和1.8%~4.2%。面膜中的脂溶性荧光增白剂C.I.162有较强的透皮能力可以进入皮下,在0~36 h内透皮扩散符合零级动力学方程;而C.I.135、C.I.185、C.I.367、C.I.368四种FWAs短期内均被皮肤吸收而未透过皮肤。结果提示,脂溶性FWAs较易迁移到皮肤的角质层或皮下,对哺乳动物皮肤没有刺激作用。

Determination of brominated diphenyl ethers in atmospheric particulate matter using selective pressurized liquid extraction and gas chromatography–mass spectrometry with a negative chemical ionization

This study describes the development and validation of a sensitive and reliable method for determination of polybrominated diphenyl ethers（PBDEs）in atmospheric particulate matter using selective pressurized liquid extraction（SPLE）and gas chromatography–mass spectrometry with a negative chemical ionization（GC-NCI-MS）.Extraction and clean-up were performed using PLE with 2 g florisil and 3 g silica placed in the extraction cells.Under optimal conditions,14 PBDEs were extracted at 70℃ using hexane/dichloromethane（50：50,v/v）as solvent.Validation of SPLE returned excellent recoveries for most analytes,with relative standard deviations mostly below20%.Method detection limits ranged from 0.13 to15.38 ng·mL^-1 for the GC-MS analyses.The method was successfully applied to atmospheric particulate matter of Beijing,where analytes were detected in the range of182.79 to 468.99 pg·m^-3.

Application of polypyrrole nanofibers in the selective extraction of methotrexate and its polyglutamate metabolites from hospital effluents

A novel solid-phase extraction(SPE)strategy based on polypyrrole(Ppy)nanofibers was developed for the determination of trace methotrexate and its polyglutamate metabolites(MTXs)in hospital effluents.Ppy was coated on the surface of electrospun polystyrene nanofibers by in situ oxidative polymerization to form Ppy electrospun nanofibers.The mechanism of adsorption on MTXs was explored through static adsorption studies.The MTX contents,after extraction,were determined by liquid chromatography-tandem mass spectrometry analysis.Results show that the physical/chemical adsorption of targets occurs on the surface of Ppy nanofibers,which is most likely dominated by multiple adsorptions and heterogeneous adsorption sites.Ppy nanofibers exhibit satisfying extraction performance.The content of targets detected in medical wastewater samples ranges from 21 to 2908 ng/L.The novel strategy based on Ppy nanofiber SPE can extract trace MTXs effectively,guarantee analytical accuracy,and circumvent the storage and transportation of water samples during on-site sampling operations.

Economic and Qualitative Traits of Italian Alps Saffron

Saffron, obtained from the flower stigmas of Crocus sativus L., is one of the most expensive food spices. The introduction of saffron in alpine areas could help to broaden and diversify the activities of mountain multifunctional farms, with a positive impact on economy and land management. According to ISO 3632(2010/2011), saffron can be classified into three categories of quality(I, II, III) depending on the concentration of the three main metabolites responsible for its characteristic colour, flavor and aroma: Crocin, Picrocrocin and Safranal. This study represents the first investigation of the quality of saffron produced in the Italian Alps evaluated with spectrophotometry, HPLC, solid-phase microextraction(SPME), and gas chromatographic analysis combined with mass spectrometry(GC/MS). The experiments used Crocus sativus stigmas produced in 2012-2013 in different areas of the Central Italian Alps were located at an altitude between 720 and 1200 m a.s.l.. Results obtained were compared to commercial saffron. The analyses confirmed that all samples can be classified in the first quality category according to the ISO classification. This high quality is also confirmed by HPLC analysis. Moreover, the SPME-GC/MS analysis identified some differences in the aromatic profile of saffron samples, in particular regarding safranal concentration. A preliminary assessment of the economic viability of high quality saffron production for local markets was also performed. Our study provides valid information regarding the quality and economic sustainability of saffron production in the alpine area confirming this crop as a good candidate for a new source of income for multifunctional farms in mountain areas.

采用HPLC-DAD-MS法去重复分析海绵Aplysina aerophoba的溴代酪氨酸衍生物

目的对海绵Aplysina aerophoba的溴代酪氨酸衍生物进行去重复分析,以期为该类新化合物的快速发现提供指导。方法采用高效液相色谱与电喷雾质谱联用技术(HPLC-DAD-MS),利用紫外吸收光谱特征和质谱数据,建立溴代酪氨酸衍生物的快速鉴别方法。结果发现16个溴代酪氨酸衍生物,其中5个化合物可能是新化合物。结论本法简便、迅速,可用于海绵中溴代酪氨酸衍生物类成分的去重复分析。

Metabolite identification and the development of a simultaneous quantification method for wogonin and wogonin-7-O-glucuronide:application to a distribution study in mice liver

Wogonin possesses potent inhibitory activities against cancer cell growth in vitro and in vivo and has attractive safety profiles.A highly sensitive liquid chromatography coupled with tandem mass spectrometry method was developed for the identification of major metabolites in mice liver after intravenous administration of wogonin.Five metabolites were identified and biotransformation pathways were elucidated as well.Furthermore,a method was developed and validated for the simultaneous quantitatively determination of wogonin and wogonin-7-O-glucuronide in mice liver.After liquid-liquid extraction by ethyl acetate,the analytes were separated on a C_（18）column with a mobile phase of methanol-10 mM ammonium acetate water （80：20,v/v）.The detection was operated with negative selected reaction monitoring mode using electrospray ionization technique. The linear response range was 0.2-40μg/g for both wogonin and wogonin-7-O-glucuronide in mice liver.The developed quantification method was suitable for distribution study after intravenous infusion of wogonin injection in animals.

Simultaneous determination of four saponins in Shugan Quzhi Capsule by UHPLC-MS/MS

Shugan Quzhi capsule is a hospital preparation of Xinhua Hospital affiliated to School of Medicine, Shanghai Jiaotong University. It has been used for the treatment of adult patients with fatty liver caused by obesity, high cholesterol and other factors. In the present study, we established an ultra-high pressure liquid chromatography-tandem mass spectrometry （UHPLC-MS/MS） method to simultaneously determine 4 saponin ingredients including Notoginsenoside R1, Ginsenoside Rbl, Ginsenoside Re and Ginsenoside Rgl present in Shugan Quzhi capsule. The chromatographic separation was conducted on ZORBAX SB-C18 （2.1 mm×50 mm, 1.8 μm）. The mobile phase was composed of acetonitrile and aqueous solution consisted of 0.05% formic acid and 5 mM ammonium acetate. Gradient elution rate was 0.3 mL/min, the column temperature was 40 ℃ MS was conducted using electrospray ionisation （ESI） and multiple reaction monitoring （MRM） coupled with positive and negative scanning switch. With which, Ginsenoside Re and Ginsenoside Rgl were detected using negative ion mode detection while Notoginsenoside R1, Ginsenoside Rbl and internal standard （Ginsenoside F1） were detected using positive ion mode detection. The limits of quantification （LOQ） for Notoginsenoside R1, Ginsenoside Rbl, Ginsenoside Re and Ginsenoside Rgl were 6.54× 10-4, 2.57×104, 0.11 and 6.91 × 10-3 ng/mL, respectively. The limits of detection （LOD） for these compounds were 1.96×10-4, 7.70×10-5, 3.45× 10-2, and 2.07× 10-3 ng/mL, respectively. All calibration curves showed a good linearity （r2〉0.9633） within the test range. The intra- and inter-day precisions （relative standard deviation, RSD） were lower than 5% and the average recoveries were in the range of 80%-120%. With this method, four kinds of saponins were separated and detected in 6 min. This method is simple, rapid and shows high sensitivity and accuracy.

Combination of reversed phase liquid chromatography and zwitterion exchange-reversed phase-hydrophilic interaction mixed-mode liquid chromatography coupled with mass spectrometry for the analysis of antibiotics and their impurities

In this study, a system involving two-dimensional, column-switching high-performance liquid chromatography （HPLC） coupled with tandem mass spectrometry （LC-MS/MS） was developed and optimized for the analysis of antibiotics and their related substances. In the first-dimensional chromatography, the analytes were separated on a zwitterion exchange-reversed phase-hydrophitic interaction （ZIC-RP-HILIC） mixed-mode column coupled with tandem mass spectrometry （LC-MS/MS）. A commonly used reversed phase LC column was employed in the second-dimensional chromatography. The mobile phase for the ZIC-RP-HILIC mixed-mode chromatography consisted of a volatile buffer that was compatible with LC-MS/MS, which enhanced the efficiency of ionization for structure elucidation. The antibiotic impurities eluted in the ion-pairing reversed phase chromatography were directly characterized by the ZIC-RP-HILIC-MS system, and the orthogonal separation of ZIC-RP-HILIC mixed-mode chromatography and reversed phase LC provided extra confidence that no impurity was missed. The efficiency of this method was demonstrated in the analysis of penicillin V potassium, oxacillin sodium, ceftriaxone sodium, and their impurities. In addition, this method is convenient for impurity profiling of antibiotics, and may be used for the analysis of other pharmaceutical ingredients.