Ultrahigh-pressure Liquid Chromatography-tandem Mass Spectrometry Research Articles

Analyzing Per- and Polyfluoroalkyl Substances (PFAS) in Foods

Environmental contaminants can affect human and animal health and are thus an issue of concern. Anthony Provatas is a Research Professor and the Organics Laboratory Manager at the University of Connecticut in the Center for Environmental Sciences and Engineering (CESE) of the Institute of the Environment; he is also Program Chair and Board Member of the Eastern Analytical Symposium (EAS). His research has been focused on the effects of contaminants on human health. We recently spoke to him about his work using ultrahigh-pressure liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS), and UHPLC–quadrupole–time-of-flight mass spectrometry (UHPLC– QTOF-MS) to analyze the presence of per- and polyfluoroalkyl substances (PFAS) in the environment, particularly in foods.

Beyond natural rubber: Taraxacum kok-saghyz and Taraxacum brevicorniculatum as sources of bioactive compounds

Taraxacum kok-saghyz (TKS) and T. brevicorniculatum (TB) are broadly investigated as natural rubber-producing plants and possible alternative supply sources for this relevant raw material. To fully exploit Taraxacum as a profitable crop, all the potential co-products should be investigated, through in-depth analysis of metabolites present in different organs of the plant. In the present study, natural rubber (NR), inulin, and resin content was measured by accelerated solvent extraction from the roots of TB and TKS, highlighting a 5-fold more content of NR in TKS compared to TB. Moreover, the chemical composition of both acetone and methanolic extracts from the roots and leaves of TKS and TB has been characterized by ultra-high-pressure liquid chromatography/tandem mass spectrometry (UHPLC-HRMS) technique and the content of target compounds between TKS and TB was also compared. The analysis resulted in the detection of 55 metabolites, whose identification was discussed based on chemical classes and the extraction method. Thus, sesquiterpenoids, fatty acids and their derivatives, phenolic compounds, mainly caftaric and chicoric acid, were identified. Hence, both the leaves and roots of TB, and especially of TKS, are rich in a wide variety of high-value-added compounds exploitable along with NR and inulin to increase the commercial value of these two dandelion species.

Persistent toxicity and dissipation dynamics of afidopyropen against the green peach aphid Myzus persicae (Sulzer) in cabbage and chili

The green peach aphid, Myzus persicae (Sulzer), is a significant global pest in horticultural and field crops. Afidopyropen is a novel systemic insecticide with high efficacy against sucking pests, and it is suitable for the management of M. persicae. However, the persistent toxicity and dissipation dynamics of afidopyropen in vegetables remain unknown. In this study, we determined the residual activity and dissipation dynamics of afidopyropen against M. persicae on cabbage and chili. The data showed that the toxicity of afidopyropen against M. persicae lasted more than 30 days; the corrected mortality was greater than 80% 10 days after application and was 50–60% 30 days post-application. The afidopyropen residues on cabbage and chili plants were quantified using ultrahigh-pressure liquid chromatography–tandem mass spectrometry. The dissipation half-lives of afidopyropen on cabbage and chili plants ranged from 1.45 to 2.34 days and 3.98–5.98 days at different recommended dosages, respectively. Our findings provide valuable data for the maximum residue limits of afidopyropen on vegetables and will help growers determine the frequency and timing of its application on cabbage and chili.

Kinetic Characteristics of Curcumin and Germacrone in Rat and Human Liver Microsomes: Involvement of CYP Enzymes.

Curcumin and germacrone, natural products present in the Zingiberaceae family of plants, have several biological properties. Among these properties, the anti-NSCLC cancer action is noteworthy. In this paper, kinetics of the two compounds in rat liver microsomes (RLMs), human liver microsomes (HLMs), and cytochrome P450 (CYP) enzymes (CYP3A4, 1A2, 2E1, and 2C19) in an NADPH-generating system in vitro were evaluated by UP-HPLC–MS/MS (ultrahigh-pressure liquid chromatography–tandem mass spectrometry). The contents of four cytochrome P450 (CYP) enzymes, adjusting by the compounds were detected using Western blotting in vitro and in vivo. The t1/2 of curcumin was 22.35 min in RLMs and 173.28 min in HLMs, while 18.02 and 16.37 min were gained for germacrone. The Vmax of curcumin in RLMs was about 4-fold in HLMs, meanwhile, the Vmax of germacrone in RLMs was similar to that of HLMs. The single enzyme t1/2 of curcumin was 38.51 min in CYP3A4, 301.4 min in 1A2, 69.31 min in 2E1, 63.01 min in 2C19; besides, as to the same enzymes, t1/2 of germacrone was 36.48 min, 86.64 min, 69.31 min, and 57.76 min. The dynamic curves were obtained by reasonable experimental design and the metabolism of curcumin and germacrone were selected in RLMs/HLMs. The selectivities in the two liver microsomes differed in degradation performance. These results meant that we should pay more attention to drugs in clinical medication–drug and drug–enzyme interactions.

A porous boron nitride nanorods-based QuEChERS analysis method for detection of five neonicotinoid pesticide residues in goji berries

To accurately determine neonicotinoid pesticide residues in goji berries, porous boron nitride nanorods (p-BNNRs) were prepared and used as a new QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) clean-up sorbent. Combined with ultrahigh-pressure liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), a modified QuEChERS method was developed to determine five neonicotinoid pesticide residues in goji berries. In goji berries, the p-BNNRs were shown to have a greater clean-up ability than typical clean-up materials (C18, PSA) The recoveries of the five targets ranged from 78.1 to 117.3% at three fortified levels, and the LODs ranged from 2.2 to 3.7 μg kg−1. The results indicate that this approach could be successfully used to quickly determine of the five neonicotinoid insecticide residues in goji berries for risk assessment purposes, demonstrating the applicability and suitability of p-BNNRs for the routine evaluation of neonicotinoid insecticide residues in goji berries.

Metabolomic profiling of fatty acid biomarkers for intracerebral hemorrhage stroke

The identification of new biomarkers (e.g., metabolic biomarkers) will facilitate not only the diagnosis of stroke but also the differentiation of stroke subtypes, especially the discrimination of ischaemic stroke from intracerebral hemorrhage. Herein, we develop for the first time an ultra-high-pressure liquid chromatography tandem mass spectrometry (UHPLC-MS)-based targeted metabolomic method to screen the metabolic biomarkers of stroke and identify the fatty acid metabolite 20-hydroxy-leukotriene B4 (20-OH-LTB4) and its key enzyme cytochrome P450 family 4 subfamily F member 2 (CYP4F2) as the potential biomarkers for differentiating healthy persons, acute ischemic stroke (AIS) patients, and intracerebral hemorrhage stroke (ICH) patients. We evaluated 158 fatty acids and their metabolites in 177 serum samples obtained from 65 healthy volunteers, 70 AIS patients and 42 ICH patients, and identified the potential biomarkers associated with ICH by using multivariate statistical analysis. We found that 20-OH-LTB4 and arachidonic acid can be used to discriminate ICH patients from healthy individuals, and 20-OH-LTB4 and 17, 18-epoxy-eicosatetraenoic acid (7,18-EpETE) can be used to differentiate the subtypes of ICH and AIS. Especially, 20-OH-LTB4 may function as a potential biomarker for ICH diagnosis and risk assessment, and it can discriminate ICH patients from healthy individuals and AIS patients. Moreover, we identified CYP4F2 protein as a potential biomarker of ICH for prevention and treatment assessment. This method may provide a powerful platform for ICH diagnosis, prevention, and treatment assessment.

Pharmacokinetic Herb-Drug Interaction between Hibiscus sabdariffa Calyces Aqueous Extract and Captopril in Rats

Hibiscus sabdariffa L. (Malvaceae) is a traditional medicinal herb widely consumed as a beverage (“hibiscus tea”), and its global popularity is expanding due to health benefits such as blood pressure and cholesterol control. Previous studies showed that Hibiscus sabdariffa is coadministered with antihypertensives and antihyperlipidemics, thus predisposing herb-drug interactions. We investigated the pharmacokinetic interaction between H. sabdariffa L. aqueous extract and captopril, a frequently prescribed antihypertensive. In this study, chemical profile of H. sabdariffa L. aqueous extract was identified using HPLC system equipped with a DAD detector at 360 nm and 520 nm. The male Sprague Dawley rats were divided into two groups of six rats. Group I received a single dose of captopril suspension (4.5 mg/200 g body weight (BW) orally (p.o.)) while group II received H. sabdariffa L. aqueous extract (60 mg/200 g BW; p.o.) daily for two weeks prior to the same captopril dose. Multiple blood samples were collected at predetermined times after captopril administration and the plasma concentration was analyzed using ultrahigh-pressure liquid chromatography-tandem mass spectrometry. Chemical profiling of the H. sabdariffa L. aqueous extract showed that the extract contains chlorogenic acid, myricetin 3-arabinogalactoside, 5-O-caffeoylshikimic acid, quercetin 3-rutinoside, delphinidin 3-sambubioside, and cyanidin 3-sambubioside. Ingestion of the extract significantly reduced the captopril area under the curve (AUC)0−t (0.1745 (0.1254–0.2429)), AUC0−∞ (0.1734 (0.1232–0.2442))], and peak plasma concentration (0.2119 (0.1337–0.3359)) (geometric mean ratio of the coadministration group to the captopril group (90% CI)). The geometric mean ratios were falling outside the 90% CI of 0.8–1.25 bioequivalent range. Conversely, H. sabdariffa L. extract increased the apparent total body clearance (Cl/F, 0.0257 ± 0.0115 vs. 0.1418 ± 0.0338 mL/h·kg) and the apparent volume of distribution (Vd/F, 0.0541 ± 0.0226 vs. 0.3205 ± 0.0790 mL/kg). This study indicated that coadministration of H. sabdariffa L. aqueous extract could change the pharmacokinetic profile of captopril; therefore, its coadministration should be avoided.

Separation and Quantification of Superwarfarin Rodenticide Diastereomers-Bromadiolone, Difenacoum, Flocoumafen, Brodifacoum, and Difethialone-in Human Plasma.

Superwarfarins, second-generation long-acting anticoagulant rodenticides, are 4-hydroxycoumarin analogues of warfarin that contain a large hydrophobic side chain. These compounds contain two chiral centers and are synthesized for commercial use as two pairs of diastereomer. To support studies of superwarfarin pharmacokinetics and other efforts to improve clinical care for poisoning victims, a quantitative assay was developed for the measurement of diastereomer of bromadiolone, difenacoum, flocoumafen, brodifacoum, and difethialone in human plasma. Based on ultrahigh-pressure liquid chromatography-tandem mass-spectrometry (UHPLC-MS/MS), this method was validated according to U.S. Food and Drug Administration (FDA) guidelines. Sample preparation involved simple protein precipitation followed by reversed phase UHPLC, which resolved all five pairs of cis/trans diastereomer in less than 10 min. Superwarfarins were measured using negative ion electrospray followed by selected-reaction monitoring on a triple quadrupole mass spectrometer. Calibration curves covered 3-4 orders of magnitude with linear regression coefficients of >0.999. The lower limits of quantitation were from 0.013 to 2.41 ng/mL, and intra-day and inter-day accuracy and precision coefficients of variation were <12%. A 10-min UHPLC-MS/MS assay was developed and validated for the separation and quantitative analysis of the pairs of diastereomer of five superwarfarins in human plasma. This method was used to identify and measure superwarfarins and their cis/trans diastereomers in plasma obtained from patients treated for coagulopathy following consumption of contaminated synthetic cannabinoid products.

Inkjet-Based Dispersive Liquid-Liquid Microextraction Method Coupled with UHPLC-MS/MS for the Determination of Aflatoxins in Wheat.

A novel method was developed for determination of aflatoxin B1, B2, G1, and G2 (AFB1, AFB2, AFG1, and AFG2) in wheat using inkjet-based dispersive liquid-liquid microextraction (DLLME) coupled with ultrahigh-pressure liquid chromatography-tandem mass spectrometry. A drop-on-demand jetting device was used to form a cloudy solution in traditional DLLME by injecting extraction solvent (10 μL) as ultrafine droplets (∼20 μm diameter) at high frequency into sample solution. The method was validated using wheat as a representative matrix, which was pretreated with acetonitrile/water solution. Good linearity was observed over the studied range (0.06-6 μg/kg), and the limits of quantification (0.06-0.18 μg/kg) were below the maximum level established by the European Union for cereal. Satisfactory recoveries, ranging from 83.2% to 93.0% with relative standard deviations below 4.6%, were obtained for all compounds. The method, which is convenient and reliable and has low solvent consumption, represents a new direction for the development of traditional DLLME technology.

Development of a modified QuEChERS method based on magnetic multiwalled carbon nanotubes for the simultaneous determination of veterinary drugs, pesticides and mycotoxins in eggs by UPLC-MS/MS.

A modified QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) method was developed for the simultaneous determination of veterinary drugs, pesticides and mycotoxins in eggs by ultrahigh-pressure liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Several extraction conditions were tested and optimized, and the obtained extraction efficiency of all the targeted compounds (particularly macrolides) could fulfill the requirements. In the purification procedure, magnetic multiwalled carbon nanotubes (Fe3O4-MWCNTs) were used as adsorbents, and an external magnet was utilized to achieve a faster adsorbent separation, compared to the traditional centrifugation process. The recoveries of all analytes were in the range of 60.5%-114.6% at three fortified levels with relative standard deviations (RSDs) of less than 20%, and the LOQs ranged from 0.1 μg·kg-1 to 17.3 μg·kg-1. This method was successfully applied to the analysis of egg samples, demonstrating its applicability and suitability for the routine analysis of multiclass residues in egg samples.

High-throughput and rapid quantification of lipids by nanoflow UPLC-ESI-MS/MS: application to the hepatic lipids of rabbits with nonalcoholic fatty liver disease

A rapid and high-throughput quantification method (approximately 300 lipids within 20min) was established using nanoflow ultrahigh-pressure liquid chromatography-tandem mass spectrometry (nUPLC-ESI-MS/MS) with selective reaction monitoring (SRM) and applied to the quantitative profiling of the hepatic lipids of rabbits with different metabolic conditions that stimulate the development of nonalcoholic fatty liver disease (NAFLD). Among the metabolic conditions of rabbits in this study [inflammation (I), high-cholesterol diet (HC), and high-cholesterol diet combined with inflammation (HCI)], significant perturbation in hepatic lipidome (>3-fold and p < 0.01) was observed in the HC and HCI groups, while no single lipid showed a significant change in group I. In addition, this study revealed a dramatic increase (>2-fold) in relatively high-abundant monohexosylceramides (MHCs), sphingomyelins (SMs), and triacylglycerols (TGs) in both the HC and HCI groups, especially in MHCs as all 11 MHCs increased by larger than 3- to 12-fold. As the levels of the relatively high-abundant lipids in the above classes increased, the total lipidome level of each class increased significantly by approximately 2-fold to 5-fold. Other classes of lipids also generally increased, which was likely induced by the increase in mitogenic and nonapoptotic MHCs and SMs, as they promote cell proliferation. On the other hand, a slight decrease in the level of apoptotic ceramides (Cers) was observed, which agreed with the general increase in total lipid level. As distinct changes in hepatic lipidome were observed from HC groups, this suggests that HC or HCI is highly associated with NAFLD but not inflammation alone itself. Graphical Abstract Schematic of lipidomic analysis from hepatic tissue using nanoflow LC-ESI-MS/MS and nUPLC-ESI-MS/MS.

Pharmacokinetics of a long-acting ceftiofur crystalline-free acid formulation in Asian elephants (Elephas maxim us)

To determine the pharmacokinetics of a long-acting formulation of ceftiofur, ceftiofur crystalline-free acid (CCFA), following SC injection to Asian elephants (Elephas maximus). 11 adult Asian elephants. Each elephant received CCFA (6.6 mg/kg, SC) in the area caudoventral to the base of an ear. Blood samples were collected from an ear vein immediately prior to and at 0.5, 1, 2, 4, 8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours after CCFA administration. Plasma concentrations of desfuroylceftiofur acetamide (the acetamide derivative of ceftiofur) were measured via ultrahigh-pressure liquid chromatography-tandem mass spectrometry. Data were analyzed via a noncompartmental pharmacokinetics approach. The mean ± SD maximum plasma concentration of desfuroylceftiofur acetamide was 1.36 ± 0.74 μg/mL and was detected at 4718 ± 31.30 hours. The mean ± SD area under the curve from time 0 to infinity was 2278 ± 55.8 μg•h/mL, and the mean residence time from time 0 to infinity was 158.2 ± 90.2 hours. The terminal elimination half-life associated with the slope of the terminal phase had a harmonic mean ± pseudo-SD of 83.36 ± 30.01 hours. Elephants tolerated CCFA at a dose of 6.6 mg/kg, SC, well. Dosing recommendations will depend on the mean inhibitory concentration of ceftiofur for each bacterial pathogen. Desfuroylceftiofur acetamide concentrations remained > 0.25 μg/mL for the entire 168-hour study period, which suggested CCFA would provide clinically relevant antimicrobial activity against certain pathogens for 7 to 10 days.

Pharmacokinetics and tissue elimination of tulathromycin following subcutaneous administration in meat goats

To determine the tissue depletion profile of tulathromycin and determine an appropriate slaughter withdrawal interval in meat goats after multiple SC injections of the drug. 16 healthy Boer goats. All goats were administered tulathromycin (2.5 mg/kg, SC) twice, with a 7-day interval between doses. Blood samples were collected throughout the study, and goats were euthanized at 2, 5, 10, and 20 days after the second tulathromycin dose. Lung, liver, kidney, fat, and muscle tissues were collected. Concentrations of tulathromycin in plasma and the hydrolytic tulathromycin fragment CP-60,300 in tissue samples were determined with ultrahigh-pressure liquid chromatography-tandem mass spectrometry. The plasma profile of tulathromycin was biphasic. Absorption was very rapid, with maximum drug concentrations (1.00 ± 0.42 μg/mL and 2.09 ± 1.77 μg/mL following the first and second doses, respectively) detected within approximately 1 hour after injection. Plasma terminal elimination half-life of tulathromycin was 61.4 ± 14.1 hours after the second dose. Half-lives in tissue ranged from 2.4 days for muscle to 9.0 days for lung tissue; kidney tissue was used to determine the withdrawal interval for tulathromycin in goats because it is considered an edible tissue. On the basis of the tissue tolerance limit in cattle of 5 ppm (μg/g), the calculated withdrawal interval for tulathromycin would be 19 days following SC administration in goats. On the basis of the more stringent guidelines recommended by the FDA, the calculated meat withdrawal interval following tulathromycin administration in goats was 34 days.

P1.23 Quantitative Detection of Discriminatory Proteins in Tissue and Serum of Ovarian Cancer Patients by Lc-Mse

ABSTRACT Purpose Using label-free UPLC-MSE quantification methods to identify proteins as well as determining their abundance in serum and microdissected ovarian cancer tissue. Methods Serum of six patients with a serous adenocarcinoma of the ovary (stage IIIB or higher) was collected before treatment. Matched controls with a serous cystadenoma of the ovary were chosen as a control group. In addition, homogeneous regions of cancer cells were isolated by laser capture microdissection (LCM). Normal ovarian epithelial cells and stroma samples were taken from matched controls. We employed label-free ultra-high pressure liquid chromatography tandem mass spectrometry (UPLC-MSE) to identify proteins and determine their absolute concentrations. Moderated t-tests were used to identify differentially expressed proteins between groups. p-values were adjusted for multiple-testing using Benjamini-Hochberg false discovery rates. Results In serum specimens, 20 differentially expressed proteins were identified by LC-MSE profiling. They include serum proteins such as apolipoprotein AI and transferrin, both exhibited a lower concentration in serum of cancer patients. Differential expression was also observed for apolipoproteins (APOA IV, APOA II and APOC III) and proteins not previously associated with ovarian cancer such as C9 and Afamin.In the tissue-lysates we identified 535 Proteins of which 332 could be reliably quantified. Of these 138 were differentially expressed proteins. Literature searches confirmed a link between ovarian cancer and 6 of these proteins, suggesting a possible role in disease progression. Of special interest was the identification of prohibitin (PHB) and cofilin-1 (CFL1). Immunohistochemical detection of CFL1 in formalin-fixed paraffin-embedded tissues showed heterogeneous expression in 50% of the serous ovarian carcinomas, whereas all the benign lesions were negative. These results demonstrate the validity of the protein quantitation results obtained by MSE.Interestingly, no overlap was found between the discriminatory proteins in serum and corresponding tissue lysates, illustrating the challenge to identify a single biomarker in the circulation reflecting ovary cancer. Conclusions Our study revealed several protein changes in serum and tissue of patients suffering from serous adenocarcinoma of the ovary. Further investigation of these proteins is warranted to establish whether they could provide new insights into disease etiology and act as potential new markers.

Abstract 4800: Quantitative detection of discriminatory proteins in tissue and serum of ovarian cancer patients by LC-MSE

Abstract Purpose: Using label-free UPLC-MSE quantification methods to identifying proteins as well as determining their abundance in serum and microdissected ovarian cancer tissue. Experimental procedures: Serum of six patients with a serous adenocarcinoma of the ovary (stage IIIB or higher) was collected before treatment. Matched control patients with a serous cystadenoma of the ovary were chosen as a control group. In addition, homogeneous regions of cells that exhibited uniform histology were isolated from cancer tissue by laser capture microdissection (LCM), normal ovarian epithelial cell samples and stroma samples were taken from matched controls. We subsequently employed label-free ultra-high pressure liquid chromatography tandem mass spectrometry (UPLC-MSE) to identify proteins and determine their absolute concentrations in serum and tissue lysates. Moderated t-tests were used to identify differentially expressed proteins between patient- and control-group. p-values were adjusted for multiple-testing using Benjamini-Hochberg false discovery rates and considered differentially expressed when &amp;lt;0.05. Summary of the data: In the serum specimens, 13 differentially expressed proteins were identified by LC-MSE profiling. Proteins with different concentrations in patients versus control sera include abundant serum proteins such as apolipoprotein AI and transferrin, both exhibited a lower concentration in serum of cancer patients. Differential expression was also observed for apolipoproteins (APOA IV, APOA II and APOC III) and other proteins that have not been associated with ovarian cancer previously such as C9 and Afamin. In the tissue-lysates we identified 535 Proteins of which 332 could be reliably quantified. Of these 56 were differentially expressed proteins of which 12 had non-overlapping standard deviations. Literature searches confirmed a link between ovarian cancer and 6 of these proteins, suggesting a possible role in disease progression. Of special interest was the identification of prohibitin (PHB) and cofilin-1 (CFL1). Immunohistochemical detection of CFL1 in formalin-fixed paraffin-embedded tissues of our patient group showed heterogeneous expression in 50% of the serous ovarian carcinomas, whereas all the benign lesions were negative. These results again demonstrate the validity of the protein quantitation results obtained by MSE. Interestingly, no overlap was found between the discriminatory proteins in serum specimens and corresponding tissue lysates, illustrating the challenge to identify a single biomarker in the circulation reflecting ovary cancer. Conclusions: Our study revealed several protein changes in serum and tissue of patients suffering from serous adenocarcinoma of the ovary. Further investigation of these proteins is warranted to establish whether they could provide new insights into disease etiology and act as potential new markers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4800. doi:1538-7445.AM2012-4800

Confirmation of drug delivery after liver chemoembolization: direct tissue doxorubicin measurement by UHPLC‐MS‐MS

Because liver cancer is rarely suitable for surgery, transcatheter arterial chemoembolization (TACE) is used for palliative therapy. In this procedure, an emulsion of doxorubicin in iodized oil is injected directly into liver tumors through a catheter positioned within the artery supplying blood flow to the tumor. At present, there is limited understanding of factors affecting the delivery and dispersion of doxorubicin within treated tumors during TACE. This study addresses the development and application of an ultrahigh-pressure liquid chromatography-tandem mass spectrometry (UHPLC-MS-MS) method for rapid confirmation of drug delivery after TACE in a rabbit VX2 liver cancer model. Doxorubicin levels in liver tumors were measured using UHPLC-MS-MS and compared with computed tomography measured levels of iodized oil, a metric used clinically to indicate drug delivery. We found that tissue drug levels determined using UHPLC-MS-MS did not correlate with the regional iodized oil concentration (vehicle) within tumors following TACE, suggesting that chemotherapeutic drugs like doxorubicin spread throughout tumors, and that lack of iodized oil staining in portions of a tumor does not necessarily indicate inadequate therapy during TACE.

Evaluation of a generic multi-analyte method for detection of >100 representative compounds correlated to emergency events in 19 food types by ultrahigh-pressure liquid chromatography–tandem mass spectrometry

A generic extraction procedure combined with triple quadrupole mass spectrometric detection was evaluated for multi-residue analysis in 19 different foods. Measurable peaks could be obtained at relevant concentrations for 108 out of a total of 127 targeted compounds representing a wide range of physicochemical properties and compound classes related to emergency situations. Recoveries were determined for all 19 foods spiked with the 108 compounds. Seventy-five percent of the compounds had extraction recoveries of 70% or higher, with no compound below 46%. Suppression or enhancement effects on the MS response of the compounds dissolved in the extracts were low, as more than 80% of them had matrix effects between −35% and +20% and no compound was below −44% compared to matrix-free standard. In a validation, all compounds could be quantified at 200μg/kg and 400μg/kg food sample and 81% of the compounds at 40μg/kg. It is concluded that the method is useful for the detection of various types of organic chemical toxicants at levels generally well below concentration thresholds for severe acute intoxication.