何首乌中核苷类成分QTRAP UPLC-MS/MS分析

目的:建立同时测定何首乌中10种核苷类成分的QTRAP UPLC-MS/MS分析方法,分析比较生何首乌和制何首乌中核苷类成分的差异。方法:采用QTRAP UPLC-MS/MS技术,Waters Atlantis T3色谱柱(2.1 mm×150 mm,3μm),流动相甲醇-5 mmol·L-1乙酸铵(含0.1%冰乙酸),0.4 m L·min-1梯度洗脱,采用正离子多反应监测模式测定何首乌商品药材中10种核苷类成分的含量。结果:10种核苷类成分具有良好的线性关系,相关系数均0.99;何首乌商品药材中核苷类成分尿苷、腺嘌呤、鸟苷、胞苷含量均较高;生何首乌与制何首乌中核苷类成分含量差异明显。结论:该方法简便、灵敏、准确。该研究为何首乌药材内在质量的评价和控制提供可靠的检测方法。     

Tetrodotoxin poisoning caused by Goby fish consumption in southeast China: a retrospective case series analysis

OBJECTIVES:

To investigate an unusual outbreak of tetrodotoxin poisoning in Leizhou, southeast China, a case series analysis was conducted to identify the source of illness.

METHODS:

A total of 22 individuals experienced symptoms of poisoning, including tongue numbness, dizziness, nausea and limb numbness and weakness. Two toxic species, Amoya caninus and Yongeichthys nebulosus, were morphologically identified from the batches of gobies consumed by the patients. Tetrodotoxin levels in the blood and Goby fish samples were detected using liquid chromatography-tandem mass spectrometry.

RESULTS:

The tetrodotoxin levels in the remaining cooked Goby fish were determined to be 2090.12 µg/kg. For Amoya caninus, the toxicity levels were 1858.29 µg/kg in the muscle and 1997.19 µg/kg in the viscera and for Yongeichthys nebulosus, they were 2783.00 µg/kg in the muscle and 2966.21 µg/kg in the viscera.

CONCLUSION:

This outbreak demonstrates an underestimation of the risk of Goby fish poisoning. Furthermore, the relationships among the toxic species, climates and marine algae present should be clarified in the future.     

银杏二萜内酯葡胺注射液中银杏内酯A、B、K与人血浆蛋白结合率的测定

目的：研究银杏二萜内酯葡胺注射液与人血浆蛋白的结合情况。方法：采用平衡透析法测定银杏二萜内酯葡胺注射液中银杏内酯A（GA）、银杏内酯B（GB）和银杏内酯K（GK）与人血浆蛋白的结合 率,以LC-MS/MS法测定透析内外液中各待测物的浓度,计算其血浆蛋白结合率。结果：血浆中其他成分对测定无干扰,各待测物在选择浓度范围内线性关系均良好,精密度及稳定性结果均符合方法学要求;样品孵育8 h后,GA、GB和GK与人血浆蛋白结合基本达到平衡,此时GA（0.34、1.70 和8.51 μg·mL^-1）与人血浆蛋白结合率为84.03%-88.11%,GB（0.62、3.09 和15.5 μg·mL^-1）与人血浆蛋白结合率为41.21%-53.56%,GK（0.04、0.20 和1.01 μg·mL^-1）与人血浆蛋白结合率为45.24%-59.59%。结论：该方法操作简便、快速,灵敏度高,能满足生物样品的分析要求。GA与血浆蛋白结合较强,GB和GK具有中等强度的蛋白结合率。     

新型抗结核化合物TBI-166在比格犬体内的生物利用度

目的：建立比格犬血浆中TBI-166的LC-MS/MS测定方法,研究比格犬口服TBI-166的血浆药代动力学特征和生物利用度。方法比格犬血浆样品中加入TBI-166和内标普萘洛尔后经乙腈沉淀蛋白。 HPLC分离采用Symmetry C8（2.1 mm×50 mm,3.5μm）柱,流动相为含0.1%甲酸的乙腈-水,梯度洗脱,流速为0.2 ml/min质谱检测采用电喷雾离子源,正离子选择反应监测（SRM）模式检测m/z 590→478（TBI-166）和m/z 260→183（普萘洛尔,内标）。应用上述LC-MS/MS方法测定比格犬口服TBI-166（3 mg/kg）和静脉注射（0.5 mg/kg）后的血浆药物浓度,用WinNonlin软件计算药代动力学参数和绝对生物利用度。结果比格犬血浆中TBI-166在2～1000 ng/ml浓度范围内线性关系良好,日内和日间精密度<10%、回收率>98.6%、无明显基质效应且血浆样品稳定性好。雌雄比格犬口服TBI-166（3mg/kg）后血药浓度分别于（4.4±3.5）和（1.4±0.5）h达峰,血药峰浓度分别为（122.0±34.6）和（65.4±2.3）ng/ml,AUC（0-t）为（2615.1±1524.4）和（897.2±318.6）h·μg/L。雌雄比格犬静注TBI-166（0.5mg/kg）后t1/2z为（112.9±25.3）和（69.6±35.3）h、CL为（0.3±0.1）和（0.2±0.1）L/（h·kg）、AUC（0-t）为（3222.4±1656.2）和（1798.0±729.2）h·μg/L。雌雄比格犬口服TBI-166生物利用度分别为13.5%和8.3%。结论本研究建立了比格犬血浆中TBI-166的LC-MS/MS测定方法,该方法准确、简便、灵敏。比格犬口服TBI-166后体内消除较慢,具有一定性别差异,生物利用度为8.3%～13.5%。     

液相色谱-串联质谱法测定大鼠血浆中黄体酮的浓度

目的建立测定大鼠血浆中黄体酮的液相色谱-串联质谱(LC-MS/MS)法。方法血浆样品采用液-液萃取法,经正己烷-二氯甲烷-异丙醇(100∶50∶5,V/V/V)提取后,以甲醇-水(75∶25,V/V)为流动相,以Hypersil ODS柱(50 mm×2.1 mm,5μm)为分析柱,采用ESI源以多反应监测(MRM)方式进行正离子检测。用于定量分析的离子反应为m/z 315.4→m/z(97.0+109.2)(黄体酮)和m/z 385.4→m/z 267.4(醋酸甲地孕酮,内标)。结果黄体酮血浆浓度测定方法的线性范围为0.5~200 ng/ml,日内、内间精密度(RSD)均<6.7%,准确度(RE)在±6.2%之间。结论该方法分析时间短、操作简便、灵敏度高、专属性强,适用于黄体酮的药动学研究。     

Cytokine-induced endogenous production of prostaglandin D2 is essential for human group 2 innate lymphoid cell activation

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Analysis of amphetamine and methamphetamine contents in seized tablets from Jazan,Saudi Arabia by liquid chromatography-mass spectroscopy (LC-MS/MS) and chemometric techniques

A number of illegal amphetamine tablets were seized from three different cities of Jazan province of southern Saudi Arabia and were analyzed for amphetamine and methamphetamine contents using LC-MS/MS technique. Analyses were performed using a previously reported method taking 0.1 M ammonium formate buffer (85%) and 15% acetonitrile with 0.1% formic acid as mobile phase with a total runtime of 12 min. This method was successfully applied for the routine analysis of amphetamine and methamphetamine in the seized tablets using amphetamine-D5 and methamphetamine-D5 as internal standards. Hierarchical cluster analysis was performed to establish the similarity between samples. The retention times (RT) for internal standard, amphetamine and methamphetamine were observed to be within 6.0–7.1 min. Ten tablet samples from each city were subjected to analysis and the amount of amphetamine in all the samples were found to be in the range of 9.07–14.77 mg, whereas, the amount of methamphetamine ranged from 0.12 to 0.24 mg in each tablet. Hierarchical cluster analysis showed presence of five clusters of samples indicating different characteristics and possible sources of amphetamine tablets. The largest cluster consisted of 15 samples which are expected to be of the same origin. Both amphetamine and methamphetamine are considered to be illegal products and their illegal trade and use is banned in many countries including Saudi Arabia. Therefore, there is an urgent need of strict regulations worldwide to check the illicit trafficking of these psychoactive substances and should be considered on priority.     

Pharmacokinetics,distribution, and excretion of sodium oligomannate,a recently approved anti-Alzheimer's disease drug in China

The National Medical Products Administration has authorized sodium oligomannate for treating mild-to-moderate Alzheimer's disease. In this study, an LC-MS/MS method was developed and validated to quantitate sodium oligomannate in different biomatrices. The plasma pharmacokinetics, tissue distribution, and excretion of sodium oligomannate in Sprague-Dawley rats and beagle dogs were systematically investigated. Despite its complicated structural composition, the absorption, distribution, metabolism, and excretion profiles of the oligosaccharides in sodium oligomannate of different sizes and terminal derivatives were indiscriminate. Sodium oligomannate mainly crossed the gastrointestinal epithelium through paracellular transport following oral administration, with very low oral bioavailability in rats (0.6%–1.6%) and dogs (4.5%–9.3%). Absorbed sodium oligomannate mainly resided in circulating body fluids in free form with minimal distribution into erythrocytes and major tissues. Sodium oligomannate could penetrate the blood-cerebrospinal fluid (CSF) barrier of rats, showing a constant area under the concentration-time curve ratio (CSF/plasma) of approximately 5%. The cumulative urinary excretion of sodium oligomannate was commensurate with its oral bioavailability, supporting that excretion was predominantly renal, whereas no obvious biliary secretion was observed following a single oral dose to bile duct-cannulated rats. Moreover, only 33.7% (male) and 26.3% (female) of the oral dose were recovered in the rat excreta within 96 h following a single oral administration, suggesting that the intestinal flora may have ingested a portion of unabsorbed sodium oligomannate as a nutrient.     

Ambient mass spectrometry for rapid diagnosis of psychoactive drugs overdose in an unstable patient

A 25-year-old man suffered from consciousness change was sent to our emergency department by friends who reported that they were not sure what had happened to him. Physical examination revealed bilateral pupils dilatation, lethargy, slurred speech, and ataxia. Computer-aided tomographic scan of the brain revealed no definite evidence of intracranial lesions. Routine laboratory tests revealed total physiological turmoil. Despite immediate commencement of aggressive treatment, the patient's condition deteriorated long before the traditional drug screen provided an answer for the identities of the multiple drugs overdose. It ended up with the need for cardiopulmonary resuscitation, but in vain. At the end of the tragic event, under the suggestion of a colleague, a portion of the patient's urine specimen was sent to our university esoteric laboratory for rapid analysis by means of a newly-developed thermal desorption-electrospray ionization-mass spectrometry. Ketamine, 3,4-methylenedioxymethamphetamine, and 3,4-methylenedioxyamphetamine were identified in the urine sample within 30 s. Conventional toxicological testing techniques like gas chromatography–mass spectrometry or liquid chromatography-mass spectrometry are currently used for identifying abused drugs. One concern is their time-consuming sample pretreatment which leads to relatively low efficiency in terms of turnaround time for revealing the identity of the consumed drugs particularly when the patients are severely overdosed. We learned a lesson from this case that a more efficient toxicological identification technique is essential to expedite the process of emergency care when the patients are so heavily overdosed that they are under critical life-threatening conditions.