Simultaneous Determination of Cis- and Trans-palmitoleic Acid in Rat Serum by UPLC-MS/MS

Simultaneous determination of geniposide, baicalin, cholic acid and hyodeoxycholic acid in rat serum for the pharmacokinetic investigations by high performance liquid chromatography–tandem mass spectrometry

A method for the rapid determination of 4-hexylresorcinol (4-HR) residue in shrimp by solid phase extraction (SPE) ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was established. 4-HR was extracted twice with methanol, and the extract was formulated into methanol-water solution (1:1). After being cleaned up and concentrated by a PRIME HLB solid phase extraction column, the sample was analyzed by UPLC-MS/MS and quantitatively determined by an external standard method. The separation was performed with a gradient system consisting of water and acetonitrile as the mobile phase. Monitoring was performed by electrospray ionization (ESI) in negative ion mode using multiple ion reaction monitoring (MRM). Good linearity was obtained in the concentration range of 1.0–100.0 μg/L, with correlation coefficients larger than 0.999. The limit of detection (LOD) was 0.25 μg/kg and the limit of quantification (LOQ) was 0.80 μg/kg. The average recoveries of 4-HR at spiked concentrations of 2.40, 6.40 and 16 μg/kg ranged from 81.35% to 94.68% with the relative standard deviations (n = 6) from 3.57% to 6.86%. The results showed that the method is simple, fast, sensitive, reliable, and reproducible; thus, it could be used as a rapid confirmation and quantitative analysis method of 4-HR residue in aquatic products.

Simultaneous quantification of venlafaxine and O-desmethylvenlafaxine in human plasma by ultra performance liquid chromatography–tandem mass spectrometry and its application in a pharmacokinetic study

Bisphenol A (BPA) is one of the most widely produced compounds in the world and was listed as a substance of very high concern by the European Chemicals Agency in 2016. Because of its toxicity, many countries and regions, including China, have banned BPA addition in feeding-bottles. And the European Union (EU) has banned BPA use in other food contact materials and thermal paper. Restrictions on BPA have contributed to the widespread use of alternatives. As the toxicity of BPA alternatives continues to be revealed, the alternatives of BPA alternatives are being developing. As the most extensive alternative for BPA, bisphenol S (BPS) was proven to have estrogen-disrupting effects and developmental toxicity of the neuroendocrine system. Therefore, BPS alternatives are used in thermal paper. In this study, alternatives to both BPA and BPS are collectively referred to as bisphenols (BPs). As a pooling matrix of many indoor chemicals, dust is an important pathway for human exposure to BPs. BPA and its alternatives are routinely detected in dust. As BPS alternatives have been detected in recycled paper and sludge, it is also very important to detected in dust. However, common analytical methods for BPs have low sensitivity and contain few BPS alternatives. Therefore, a high-throughput, high-accuracy, and high-sensitivity method must be established for the determination of BPs in dust; this will lay the foundation for subsequent studies on the environmental behavior and exposure risk of BPs. In this study, an ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed for the simultaneous determination of 26 variations of BPs in dust. UPLC-MS/MS parameters of the variations were optimized to compare the separation effect and response intensity in different columns and mobile phases. The influence of the extraction solvent and solid phase extraction (SPE) on the extraction efficiency and purification effect of target compounds were optimized by using the isotopic internal standard method, and the 26 variations of BPs in dust was quantitatively analyzed. Finally, the dust samples were extracted by using 3 mL of acetonitrile and 3 mL of a 50% methanol aqueous solution in an ultrasound bath. The combined extract was further purified by using an Oasis HLB cartridge (60 mg/3 mL). The cartridge was then washed with a 40% methanol aqueous solution (0.5 mL) and eluted with methanol (2 mL). The target compounds were separated on a CORTECS® UPLC® C18 column (100 mm×2.1 mm, 1.6 μm), with methanol and 1 mmol/L ammonium fluoride solution as mobile phases and a flow rate of 0.3 mL/min. Electrospray ionization (ESI) was applied in the positive, negative, and multiple reaction monitoring (MRM) modes for the mass scan. Under optimized conditions, the linear ranges of the 26 targets behaved well linearly in their respective ranges with correlation coefficients (r2)>0.999. The limits of detection (LODs) and limits of quantification (LOQs) were assessed using signal-to-noise (S/N) ratios of 3 and 10, respectively. The LODs and LOQs of the method were 0.01-0.75 μg/kg and 0.02-2.50 μg/kg, respectively. The accuracy of the method was evaluated by conducting a recovery test at three spiked levels: LOQ, two times the LOQ, and 10 times the LOQ, with the average recoveries ranging from 83.7% to 114.9%. The precision of the method was evaluated by using the relative standard deviation (RSD). The intra-day RSDs and inter-day RSDs were 0.86%-9.79% (n=6) and 5.16%-19.5% (n=6), respectively. The established method was used to determine 11 dust samples. Fifteen BPs were detected at a detection rate of 9.1%-100.0%. The detection rate for BPA, BPS, bisphenol F (BPF), 4-hydroxy-4'-isopropoxydiphenylsulfone (BPSIP), and diphenyl sulfone (DPS) was 100.0%. BPSIP, 4-allyloxy-4'-hydroxydiphenyl sulfone (BPS-MAE), and bis-(3-allyl-4-hydroxyphenyl) sulfone (TGSA) were first detected in Chinese dust, whereas 4-benzyloxy-4'-hydroxydiphenyl sulfone (BPS-MPE), 4-hydroxybenzoic acid benzyl (PHBB), and DPS were first detected in dust samples worldwide. This method is simple, rapid, and sensitive, and is suitable for the qualitative screening and quantitative analysis of the 26 BPs in dust samples.

A method has been developed for the simultaneous determination of the 10 kinds of 121 veterinary drugs (including chloramphenicols, β-agonists, sulfonamides, 4-quinolones, nitroimidazoles, macrolides, avermections, polyether antibiotics, tetracycline antibiotics, cephalosporins, etc.) in pork using QuEChERS method coupled with ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The drugs were extracted with Na2EDTA-McIlvaine buffer solution (pH = 4) and acetonitrile. Anhydrous sodium sulfate was used for the salting-out process. The solutions divided into two groups were cleaned-up by different mixed sorbents. The drugs were analyzed by UPLC-MS/MS in multiple reaction monitoring (MRM) mode via electrospray ionization. Among the 121 drugs, 5 drugs were quantified by internal standard method, and the other 116 drugs were quantified by external standard method. The calibration curves of the 121 drugs were linear in the range of 0.02-40 μg/L with the correlation coefficients more than 0.99. The limits of quantification (LOQs, S/N = 10) were 0.05-10 μg/kg. The average recoveries of 8 drugs at LOQ level in pork ranged from 41.7% to 59.6% with the relative standard deviations (RSDs) of 1.7% - 13.5%. The average recoveries of 10 drugs at LOQ level in pork ranged from 122.6% to 163.2% with the RSDs of 0.6% -14.8%. The average recoveries of 103 drugs at LOQ level in pork ranged from 60.3% to 118.3% with the RSDs of 0.4% - 16.7%. The proposed method is rapid, simple, sensitive, reliable and cost-effective.

Organic phosphate esters （OPEs） and phthalate esters （PAEs） are two classes of synthetic compounds widely incorporated into various industrial and consumer products as flame retardants and plasticizers. Both exhibit multi-organ cumulative toxicity. In this study， an ultra performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） method was developed for the determination of 22 OPEs and their diester metabolites （mOPEs） and 11 phthalate ester metabolites （mPAEs） in whole blood. The whole blood samples were extracted with 0.1% formic acid-acetonitrile by liquid-liquid extraction for protein precipitation， and then purified by HMR S-micro BIO 96-well solid phase extraction column. The filtrate was blown to near dryness with nitrogen， and reconstituted with 0.1% formic acid-acetonitrile solution. The target compounds were detected by UPLC-MS/MS. A Ghost Trap DS-HP chromatographic column （30 mm×2.1 mm） was used as the background ghost peak trap column， and an ACQUITY UPLC^® BEH C18 chromatographic column （150 mm×2.1 mm， 1.7 μm） was used as the analytical column. Methanol and 0.5 mmol/L ammonium acetate were used as mobile phase for gradient elution. Electrospray ionization （ESI） was used for MS detection， with both positive and negative ion scanning in the multiple reaction monitoring （MRM） mode. Isotope internal standard method was used for quantification. The results showed that 33 target compounds could be separated within 15 min， and good linear relationships were observed for all target compounds across their respective mass concentration ranges （<italic>r</italic>=0.993 3-0.999 8）. The limits of detection were 0.003-0.31 ng/mL and the limits of quantification were 0.01-1.02 ng/mL. The spiked recoveries of 33 targets in whole blood samples ranged from 60.5% to 138.3%， with relative standard deviations （RSDs） from 1.6% to 11.0%. The detection rates of tris-（2-Chloroisopropyl）phosphate （TCiPP）， triphenyl phosphate （TPHP）， 2-ethylhexyl diphenyl （EHDPP）， mono（2-ethyl-5-hydroxyhexyl） phthalate （MEHHP）， mono-n-butyl phthalate （MNBP） and mono-n-octyl phthalate （MOP） were 100% in 14 whole blood samples， and the highest detection amount of TPHP was 10.04 ng/mL. The developed method is simple to operate， sensitive， accurate， requires small sample volumes， and is cost-effective on reagents. It is suitable for human biomonitoring， and provides a theoretical basis for monitoring organic phosphate and phthalic ester substances in the population.

At present, new prohibited substances are becoming more common illegal additions in cosmetics. Clobetasol acetate is a new glucocorticoid, which is not covered in the current national standards and is a homologue of clobetasol propionate. A method was established for the determination of clobetasol acetate as a new glucocorticoid (GC) in cosmetics by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Five common cosmetic matrices were suitable for this new method: creams, gels, clay masks, masks and lotions. Four pretreatment methods were compared: direct extraction by acetonitrile, PRiME pass-through column purification, solid-phase extraction (SPE) purification, and QuEChERS purification. Further, the effects of different extraction efficiencies of the target compound, such as extraction solvents and extraction time, were investigated. The MS parameters, such as ion mode, cone voltage and collision energy of ion pairs of the target compound, were optimized. The chromatographic separation conditions and response intensities of the target compound in different mobile phases were compared. Based on the experimental results, the optimal extraction method was determined to be direct extraction, wherein the samples were vortex dispersed with acetonitrile, ultrasonic extraction over 30 min and filtered by a 0.22 μm organic millipore filter, and then the samples were detected by UPLC-MS/MS. The concentrated extracts were separated on a Waters CORTECS C18 column (150 mm×2.1 mm, 2.7 μm), where the water and acetonitrile were used as the mobile phases for gradient elution. The target compound was detected with the multiple reaction monitoring (MRM) mode under electrospray ionization and positive ion scanning (ESI+). Quantitative analysis was performed by matrix matching standard curve. Under the optimum conditions, the target compound had good linear fitting in the range of 0.9-37 μg/L. The linear correlation coefficient (R2) was greater than 0.99, the limit of quantification (LOQ) of the method was 0.09 μg/g and the limit of detection (LOD) was 0.03 μg/g for these five different cosmetic matrices. The recovery test was conducted under three spiked levels: 1, 2 and 10 times of LOQ. The recoveries of the tested substance were between 83.2% and 103.2% in these five cosmetic matrices, and the relative standard deviations (RSDs, n=6) were between 1.4% and 5.6%. This method was used to screen cosmetic samples of different matrix types, and a total of five positive samples were found, in which the content range of clobetasol acetate was from 1.1 to 48.1 μg/g. In conclusion, the method is simple, sensitive and reliable, and is suitable for high-throughput qualitative and quantitative screening, and the analysis of cosmetics with different matrix types. Moreover, the method provides crucial technical support and a theoretical basis for the establishment of feasible detection standards for clobetasol acetate in China, as well as for the control of the compound in cosmetics. This method has important practical significance to implement management measures of illegal additions in cosmetics.

A method for the determination of sulfonamide potentiators, trimethoprim (TMP), diaveridine (DVD) and ormetoprin (OMP), in different animal origin food matrices (including chicken muscle, fish muscle, chicken liver, egg and milk) has been developed by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The sample was extracted by formic acid-acetonitrile (1:9, v/v), cleaned-up by hexane, separated on an Acquity UPLC BEH C18 column (50 mm x 2.1 mm, 1.7 microm) with gradient elution. The determination was carried out with electrospray ion source under the positive mode and multiple reaction monitoring (MRM) mode. The extraction recoveries of three extraction solvents were observed. The purification condition and concentration condition were optimized. In addition, the mobile phase, column temperature and solid phase extraction column were studied. The calibration curves showed a good linearity in the range of 1.25-30.0 microg/L, and the correlation coefficients (r) were higher than 0.99. The limits of quantification (LOQ, S/N = 10) of the three potentiators were 5.0 microg/kg. At the spiked levels of 5.0, 10.0 and 20.0 microg/kg, the recoveries of the three potentiators were ranged from 61.2% to 108.5%, and the relative standard deviations (RSD, n = 6) ranged from 1.1% to 9.8%. The results indicate that the method is simple, rapid, sensitive and suitable for the qualitative and quantitative analysis of the three potentiators in multiple matrices.

Simultaneous determination of β-lactam antibiotics and β-lactamase inhibitors in bovine milk by ultra performance liquid chromatography-tandem mass spectrometry

Determination of palonosetron in human plasma by ultra performance liquid chromatography–tandem mass spectrometry and its application to a pharmacokinetic study

To develop a method for the determination of beauvercin(BEA), enniatin A(ENNA), enniatin A1(ENNA1), enniatin B(ENNB) and enniatin B1(ENNB1) in rice flour and wheat flour by ultra performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS). Samples were extracted by acetonitrile-water, purified by Oasis Prime HLB solid-phase extraction column. The sample solution was separated by waters BEH C_(18) column(2.1 mm×100 mm, 1.8 μm). The detection was performed in the electrospray positive ionization(ESI+) under multiple reaction monitoring(MRM) mode. The internal standard method and the matrix-matched calibrations were used for quantification. The linear relationships of BEA and 4 kinds of enniatins(ENNs) were good in the range of 0.1-50.0 ng/mL(r&gt;0.999). The average recoveries of BEA and ENNs in rice flour and wheat flour were 96.4%-105.4% and 99.1%-109.2%, with the relative standard deviations(RSD) of 1.01%-7.42% and 1.09%-9.69%(n=6). The detection limits(LOD) of BEA and ENNs were 0.03 μg/kg. The quantitative limits(LOQ) of BEA and ENNs were 0.1μg/kg. The matrix induced suppression or enhancement effect were 72.7%-99.3% and 60.8%-100.4%, respectively. The levels of emerging BEA and ENNs in wheat flour were higher than rice flour. The detection rate of enniatin B was highest in wheat flour and rice flour, the contents were 0.03-9.57 μg/kg and 0.03-0.56 μg/kg, the positive percentage were 98.5% and 36.4%. The method is quick, easy, accurate and sensitive, which is suitable for the determination of BEA and 4 kinds of ENNs in rice flour and wheat flour.

建立了同时测定地表水中8种双酚类物质(BPs)的超高效液相色谱-串联质谱(UPLC-MS/MS)分析方法。方法基于QuEChERS处理技术,选用乙酸乙酯为提取剂,从基质效应(ME)和萃取回收率(RE)两方面对过程效率(PE)进行优化,确定了50 mg N-丙基乙二胺(PSA)和50 mg石墨化炭黑(GCB)混合吸附剂为净化剂。8种BPs使用Waters ACQUITY UPLC BEH C18色谱柱(100 mm×2.1 mm, 1.7 μm)进行分离,以甲醇和0.1 mmol/L碳酸氢铵水溶液为流动相进行梯度洗脱,在电喷雾电离(ESI)源、负离子扫描及多反应监测(MRM)模式下进行质谱监测,基质匹配外标法定量。结果表明,8种BPs在8 min内完成色谱分离分析,在各自线性范围内线性关系良好,决定系数(R2)均大于0.9990,检出限(LOD)和定量限(LOQ)分别为0.1~2.3 ng/L和0.3~6.1 ng/L;以河水为样品基质,在不同添加水平下,8种BPs的平均加标回收率为78.8%~116.6%,相对标准偏差(RSD)为1.8%~9.0%。将该方法用于分析嘉陵江广元段及其支流中BPs的污染状况,结果显示,双酚A(BPA)检出率100%,含量为6.15 ~ 90.03 ng/L;双酚S(BPS)检出率91%,含量为未检出(nd)~4.63 ng/L。研究建立的方法实现了BPs在水中的快速富集与净化,具有简便、快速、灵敏度高和成本低廉等优势,可用于湖泊、河流等地表水中痕量BPs的快速检测。该方法的建立为我国地表水中BPs检测标准的制订和水质安全监控提供了参考。

There is an increasing trend in the consumption of extra virgin olive oil, owing to its health benefits. These health benefits are mainly correlated to health-promoting phenolic components. The aim of this study was to characterize the phenolic compositions of extra virgin olive oils (EVOOs) obtained from Delice and Memecik olive varieties from the south Aegean coastal area of Turkey by ultrasonic-assisted extraction method using ultra performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS). EVOO samples were analyzed by a rapid and effective UPLC-MS/MS equipped with electrospray ionization. UPLC analysis results showed that luteolin was high quantity, and p-coumaric acid, vanillic acid, and caffeic acid were detected in abundant amounts.

Quantitative determination of isradipine in dog plasma by an ultra performance liquid chromatography–tandem mass spectrometry method

Simultaneous determination of shanzhiside methyl ester, 8-O-acetylshan- zhiside methyl ester and luteolin-7-O-β-D-glucopyranoside in rat plasma by ultra performance liquid chromatography-tandem mass spectrometry and its application to a pharmacokinetic study after oral administration of Lamiophlomis rotata Pill.