Jing Qiu

Simultaneous determination of 14 antiviral drugs and relevant metabolites in chicken muscle by UPLC–MS/MS after QuEChERS preparation

A fast method for the simultaneous determination of 14 antiviral drugs and relevant metabolites in chicken muscle by ultra-high liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was developed. The analytes included anti-influenza drugs (amantadine, rimantadine, oseltamivir, oseltamivir carboxylate, memantine, arbidol, and moroxydine), anti-herpes drugs (acyclovir, ganciclovir, famciclovir, penciclovir, ribavirin and its main metabolite TCONH2), and an immunomodulator (imiquimod). The samples were pretreated using a modified QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) method. The determination of the target compounds was conducted in less than 11.0min, and specificity was ensured by the use of multiple reaction monitoring (MRM) acquisition mode. Good linearities (R(2)>0.9928) were obtained in the range of 0.1-100μg/L, and the recovery rates were 56.2-113.4% with RSDs of 1.7-10.3% for intra-day precision and 2.4-8.8% for inter-day precision. The LODs and LOQs of all analytes were in the ranges of 0.02-1.0 and 0.05-2.5μg/kg, respectively. An analysis of real samples suggested that this method is simple, sensitive, reliable and practical for the detection of antiviral drugs in animal tissue.

Simultaneous stereoselective detection of chiral fungicides in soil by LC–MS/MS with fast sample preparation

An enantioselective method was developed for the simultaneous detection of five chiral fungicides in soil, including fenbuconazole (1), tetraconazole (2), nuarimol (3), triticonazole (4), and simeconazole (5) by LC-MS/MS on a chiral stationary phase of cellulose tris-(3-chloro-4-methylphenylcarbamate) with a gradient elution. A new multifunctional filter was designed to simplify the QuEChERS (where QuEChERS is quick, easy, cheap, effective, rugged, and safe) method by simultaneous cleanup and filtration when the sample extracts were directly passed through it. Good linearities (R2 > 0.9980) were obtained in the range 0.005-2.5 mg/L, and the recovery rates were 77.4-103.6% with RSDs of 0.7-12.2% for intraday precision and 1.2-11.0% for interday precision. The LODs and LOQs for all enantiomers were in the range 0.1-0.2 and 0.25-0.5 μg/kg, respectively. The analysis of the incubated soil suggests that this method is reliable and practical for the stereoselective detection of chiral fungicides.

Simultaneous determination of amantadine, rimantadine and chlorpheniramine in animal-derived food by liquid chromatography-tandem mass spectrometry after fast sample preparation

A fast method for simultaneous determination of amantadine, rimantadine, and chlorpheniramine in seven animal derived samples including pork, chicken, duck, pig liver, chicken liver, pig kidney, and egg was developed using liquid chromatography-tandem mass spectrometry, and employed a new multifunctional syringe filter that makes the cleanup procedure simple and rapid based on the QuEChERS (quick, easy, cheap, effective, rugged and safe) method. The method was validated using amantadine-d15, rimantadine-d4 and chlorpheniramine-d6 as internal standards for three analytes. Good linearities (R2 > 0.9938) were obtained over the concentration range from 2 μg L−1 to 200 μg L−1 for amantadine and rimantadine, and from 0.2 μg L−1 to 20 μg L−1 for chlorpheniramine. The precision was evaluated by intra- and inter-day assays and the relative standard deviations were all within 9.85%. Mean recoveries ranged from 89.9% to 105%. The limits of detection and quantification were 0.5 and 1.0 μg kg−1 for both amantadine and rimantadine, and 0.05 and 0.1 μg kg−1 for chlorpheniramine, respectively. The application of the developed method in real samples showed that amantadine and chlorpheniramine were respectively detected with percentages of 3.7% and 0.3% in all tested samples.

Enantioselective accumulation of chiral polychlorinated biphenyls in lotus plant (Nelumbonucifera spp.)

Enantioselective accumulation of chiral polychlorinated biphenyls (PCBs) 91, 95, 136, 149, 176 and 183 was investigated in lotus plants (Nelumbonucifera spp.) exposed to these chemicals via spiked sediment, to determine uptake and possible biotransformation for aquatic phytoremediation purposes. The concentrations of most PCBs were greatest in roots at 60 d (19.6 ± 1.51-70.6 ± 6.14 μg kg(-1)), but were greatest in stems and leaves at 120 d (25.3 ± 6.14-95.5 ± 19.4 μg kg(-1) and 17.4 ± 4.41-70.4 ± 10.4 μg kg(-1), respectively). Total amounts were greatest at 120 d and significantly higher in roots than those in stems and in leaves (1,457 ± 220-5,852 ± 735 ng, 237 ± 47.1-902 ± 184 ng and 202 ± 60.3-802 ± 90.2 ng, respectively), but represented less than 0.51% of the total mass of PCBs added to sediments, indicating that lotus plants were unlikely to remove appreciable amounts of PCBs from contaminated sediments. Racemic PCB residues in sediment indicate no enantioselective biodegradation by sedimentary microbial consortia over the entire experiment. Preferential accumulation of the (-)-enantiomers of PCBs 91, 95 and 136 were observed in roots, stems and leaves, but non-enantioselective accumulation was observed for PCBs 149, 176 and 183. These results indicate that aquatic plants can accumulate PCBs enantioselectively via root uptake, possibly by biotransformation within plant tissues as observed for terrestrial plants. This is also the first report to identify optical rotation of the atropisomers of PCBs 91 and 95.

Analysis of the Enantioselective Effects of PCB95 in Zebrafish (Danio rerio) Embryos through Targeted Metabolomics by UPLC-MS/MS.

As persistent organic pollutants, polychlorinated biphenyls (PCBs) accumulate in the bodies of animals and humans, resulting in toxic effects on the reproductive, immune, nervous, and endocrine systems. The biological and toxicological characteristics of enantiomers of chiral PCBs may differ, but these enantioselective effects of PCBs have not been fully characterized. In this study, we performed metabolomics analysis, using ultra-high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) to investigate the enantioselective toxic effects of PCB95 in zebrafish (Danio rerio) embryos after exposure to three dose levels of 0.1, 1, and 10 μg/L for 72 h. Multivariate analysis directly reflected the metabolic perturbations caused by PCB95. The effects of (-)-PCB95 and (+)-PCB95 were more prominent than those of the racemate in zebrafish embryos. A total of 26 endogenous metabolites were selected as potential marker metabolites with variable importance at projection values larger than 1 and significant differences (p<0.05). These metabolites included amino acids, organic acids, nucleosides, betaine, and choline. The changes in these biomarkers were dependent on the enantiomer-specific structures of PCB95. Fifteen metabolic pathways were significantly affected, and several nervous and immune system-related metabolites were significantly validated after exposure. These metabolic changes indicated that the toxic effects of PCB95 may be associated with the interaction of PCB95 with the nervous and immune systems, thus resulting in disruption of energy metabolism and liver function.

Chiral PCB 91 and 149 Toxicity Testing in Embryo and Larvae (Danio rerio): Application of Targeted Metabolomics via UPLC-MS/MS.

In this study, we aimed to investigate the dysfunction of zebrafish embryos and larvae induced by rac-/(+)-/(−)- PCB91 and rac-/(−)-/(+)- PCB149. UPLC-MS/MS (Ultra-performance liquid chromatography coupled with mass spectrometry) was employed to perform targeted metabolomics analysis, including the quantification of 22 amino acids and the semi-quantitation of 22 other metabolites. Stereoselective changes in target metabolites were observed in embryos and larvae after exposure to chiral PCB91 and PCB149, respectively. In addition, statistical analyses, including PCA and PLS-DA, combined with targeted metabolomics were conducted to identify the characteristic metabolites and the affected pathways. Most of the unique metabolites in embryos and larvae after PCB91/149 exposure were amino acids, and the affected pathways for zebrafish in the developmental stage were metabolic pathways. The stereoselective effects of PCB91/149 on the metabolic pathways of zebrafish embryos and larvae suggest that chiral PCB91/149 exposure has stereoselective toxicity on the developmental stages of zebrafish.

Enantio-alteration of gene transcription associated with bioconcentration in adult zebrafish (Danio rerio) exposed to chiral PCB149.

Enantioselective enrichment of chiral PCB149 (2,2’,3,4’,5’,6-hexachlorobiphenyl) was analysed in adult zebrafish (Danio rerio) exposed to the racemate, (−)-PCB149, and (+)-PCB149. Greater enrichment of (−)-PCB149 compared to (+) PCB149 was observed following 0.5 ng/L exposure; however, as the exposure time and concentration increased, racemic enrichment was observed in adult fish exposed to the racemate. No biotransformation between the two isomers was observed in fish exposed to single enantiomers. When zebrafish were exposed to different forms of chiral PCB149, enantioselective expression of genes associated with polychlorinated biphenyls (PCBs) was observed in brain and liver tissues and enantioselective correlations between bioconcentration and target gene expression levels were observed in brain and liver tissues. The strong positive correlations between expression levels of target genes (alox5a and alox12) and PCB149 bioconcentration suggest that prolonged exposure to the racemate of chiral PCB149 may result in inflammation-associated diseases. Prolonged exposure to (−)-PCB149 may also affect metabolic pathways such as dehydrogenation and methylation in the brain tissues of adult zebrafish. Hepatic expression levels of genes related to the antioxidant system were significantly negatively correlated with bioconcentration following exposure to (+)-PCB149.

Multi-residue determination of 210 drugs in pork by ultra-high-performance liquid chromatography–tandem mass spectrometry

This paper presents a multi-residue analytical method for 210 drugs in pork using ultra-high-performance liquid chromatography-Q-Trap tandem mass spectrometry (UPLC-MS/MS) within 20min via positive ESI in scheduled multi-reaction monitoring (MRM) mode. The 210 drugs, belonging to 21 different chemical classes, included macrolides, sulfonamides, tetracyclines, β-lactams, β-agonists, aminoglycosides, antiviral drugs, glycosides, phenothiazine, protein anabolic hormones, non-steroidal anti-inflammatory drugs (NSAIDs), quinolones, antifungal drugs, corticosteroids, imidazoles, piperidines, piperazidines, insecticides, amides, alkaloids and others. A rapid and simple preparation method was applied to process the animal tissues, including solvent extraction with an acetonitrile/water mixture (80/20, v/v), defatting and clean-up processes. The recoveries ranged from 52% to 130% with relative standard deviations (RSDs)<20% for spiked concentrations of 10, 50 and 250μg/kg. More than 90% of the analytes achieved low limits of quantification (LOQs)<10μg/kg. The decision limit (CCα), detection capability (CCβ) values were in the range of 2-502μg/kg and 4-505μg/kg, respectively. This method is significant for food safety monitoring and controlling veterinary drug use.

Determination of Polychlorinated Biphenyl Enantiomers in Lotus Root and Sediment by Chiral Gas Chromatography-Mass Spectrometry

Abstract An enantioselective method was developed for the separation and determination of six chiral polychlorinated biphenyls (PCBs) including PCB 91, 95, 136, 149, 176 and 183 in lotus root, stem, leaf and sediment by gas chromatography-mass spectrometry (GC-MS). After optimization of instrumental parameters for enantiomeric separation and investigation of sample preparation steps including accelerated solvent extraction (ASE) parameters, extraction solvents and cleanup methods, PCB atropisomers were extracted from samples by ASE with n -hexane/acetone (1:1, V / V ) at 100 (C and 10.3 MPa for 10 min. The extracts were cleaned with sulfuric acid, purified by Florisil solid phase extraction, reconstituted with isooctane after concentration, and detected by GC-MS with Chirasil-Dex and BGB-172 columns. Good linearity was obtained in the concentration range of 0.5–100 μg L −1 for all analytes. The recoveries of spiked samples at 0.25, 2.5 and 25 μg kg −1 were 82.8%–117.0% with relative standard deviations (RSDs) of 1.5%–13.6%. The limits of detection (LOD) and limits of quantification (LOQ) were 0.01–0.02 μg kg −1 and 0.025–0.04 μg kg −1 , respectively. Chiral PCBs were not detected in lotus roots from markets, but higher concentrations were found in lotus root and sediment from a contaminated area. The concentrations of the second-eluted PCB 91, first-eluted PCB 95 and (+)-PCB 136 atropisomers in lotus root, stem and leaf were higher than those of their respective antipodes, while no significant differences between the two enantiomers of PCB 149, 176 and 183 were found.

Enantioselective Toxicity in Adult Zebrafish (Danio rerio) Induced by Chiral PCB91 through Multiple Pathways

This study aimed to further investigate the toxic mechanism of chiral polychlorinated biphenyl (PCB) 91 in adult zebrafish ( Danio rerio) exposed to racemic (rac-), (+)-, or (-)-PCB91 for 63 days. The enantioselective mortalities of adult zebrafish exposed to rac-/(+)-/(-)-PCB91 were 95.86, 50.08, and 81.50%, respectively. Tubular necrosis and cellular hypertrophy occurred in the kidneys of (-)-PCB91-treated groups, whereas demyelination and immune cell infiltration occurred in brains of the rac-, (+)-, and (-)-PCB91-treated groups. Additionally, exposure to chiral PCB91 enantioselectively induced neurotoxicity, apoptosis, and inflammation in brain tissues owing to perturbations of gene expression, protein content and sphingolipid levels. The high mortality after rac-/(+)-PCB91 exposure might be due to toxic effects on brain tissue, while the high mortality after (-)-PCB91 exposure might be due to toxic effects on kidney as well as brain tissues. Thus, our findings offer an important reference for elucidating the enantioselective toxicological mechanism of chiral PCBs in aquatic organisms.