Negative Electrospray Tandem Mass Spectrometry Research Articles

Determination of Salicylic Acid in Feed Using LC-MS/MS.

IntroductionSalicylic acid is a derivative of benzoic acid and occurs in nature. The main target of this study was to develop the liquid chromatography coupled with tandem mass spectrometry technique as a method for determination of salicylic acid in feed materials and compound feed.Material and MethodsSalicylic acid was extracted from feed with 0.1% hydrochloric acid in methanol. Separation was achieved in 8 min in a gradient elution using 0.1% formic acid and acetonitrile. The analyte was detected using negative electrospray tandem mass spectrometry. The procedure was validated to the specifications of the European Commission Decision No. 2002/657/EC.ResultsThe validation results showed the repeatability of the method, which was evaluated at three levels (0.25, 0.5, and 1.0 mg/kg). Calibration curves for the working ranges were linear (R2 0.9911 to 0.9936), and recoveries ranged from 98.3% to 101%. The LOD and LOQ for compound feed were 0.02 and 0.05 mg/kg, respectively. Salicylic acid was found mostly in corn, and its concentrations differed depending on whether it was young or fully grown (5.30–12.8 mg/kg and 0.13–1.01 mg/kg, respectively).ConclusionsA sensitive and reliable method for the determination of salicylic acid in feed and compound feed using LC-MS/MS was developed.

Analysis of Hydroxy Fatty Acids from the Pollen of Brassica campestris L. var. oleifera DC. by UPLC-MS/MS.

Ultraperformance liquid chromatography coupled with negative electrospray tandem mass spectrometry (UPLC-ESI-MS/MS) was used to determine 7 hydroxy fatty acids in the pollen of Brassica campestris L. var. oleifera DC. All the investigated hydroxy fatty acids showed strong deprotonated molecular ions [M–H]−, which underwent two major fragment pathways of the allyl scission and the β-fission of the alcoholic hydroxyl group. By comparison of their molecular ions and abundant fragment ions with those of reference compounds, they were tentatively assigned as 15,16-dihydroxy-9Z,12Z-octadecadienoic acid (1), 10,11,12-trihydroxy-(7Z,14Z)-heptadecadienoic acid (2), 7,15,16-trihydroxy-9Z,12Z-octadecadienoic acid (3), 15,16-dihydroxy-9Z,12Z-octadecadienoic acid (4), 15-hydroxy-6Z,9Z,12Z-octadecatrienoic acid (5), 15-hydroxy-9Z,12Z- octadecadienoic acid (6), and 15-hydroxy-12Z-octadecaenoic acid (7), respectively. Compounds 3, 5, and 7 are reported for the first time.

Increasing levels of long-chain perfluorocarboxylic acids (PFCAs) in Arctic and North Atlantic marine mammals, 1984–2009

Temporal variations in concentrations of perfluorinated carboxylic acids (PFCAs) and sulfonic acids (PFSAs), including perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) structural isomers, were examined in livers of pilot whale ( Globicephala melas), ringed seal ( Phoca hisida), minke whale ( Balaenoptera acutorostrata), harbor porpoise ( Phocoena phocoena), hooded seal ( Cystophora cristata), Atlantic white-sided dolphin ( Lagenorhynchus acutus) and in muscle tissue of fin whales ( Balaenoptera physalus). The sampling spanned over 20 years (1984–2009) and covered a large geographical area of the North Atlantic and West Greenland. Liver and muscle samples were homogenized, extracted with acetonitrile, cleaned up using hexane and solid phase extraction (SPE), and analyzed by liquid chromatography with negative electrospray tandem mass spectrometry (LC-MS/MS). In general, the levels of the long-chained PFCAs (C9–C12) increased whereas the levels of PFOS remained steady over the studied period. The PFOS isomer pattern in pilot whale liver was relatively constant over the sampling years. However, in ringed seals there seemed to be a decrease in linear PFOS (L-PFOS) with time, going from 91% in 1984 to 83% in 2006.

A comparative study on oxidative damage and distributions of perfluorooctane sulfonate (PFOS) in mice at different postnatal developmental stages

Effects of perfluorooctane sulfonate (PFOS) on maleic dialdehyde (MDA) content, superoxide dismutase (SOD) activity and total antioxidation capability (T-AOC) were compared in mice at different postnatal developmental stages, and concentrations and distributions of PFOS in different tissues were measured simultaneously. The male and female mice at postnatal day (PD) 7, PD 14, PD 21, PD 28 and PD 35 were distributed randomly to dosage group (50 mg/kg body weight) and control group (0 mg/kg body weight). Mice were administered with PFOS by once subcutaneous injection. Subsequently, after 24 hr, MDA content, SOD activity and T-AOC in brain and liver were analyzed. The PFOS concentrations in blood, brain and liver were determined by high-performance liquid chromatography negative electrospray tandem mass spectrometry (LC-MS). PFOS induced degression of the body weights of mice evidently and increase of relative weights of liver. Meanwhile, it depressed the SOD activity and T-AOC in brain and liver. The concentrations and distribution percentages of PFOS in blood, brain and liver of mice were significantly different at various postnatal developmental stages. Achieved results in this study indicate that younger mice pups were more sensitive to PFOS exposure. In addition, significant distinctions in concentrations and distribution percentages of PFOS in various tissues were demonstrated in this study. The gender difference observed was greater in the older mice. Thus it is worth giving attention especially to adverse effects of PFOS on foetus and children.

Analysis of triptophenolide and its related compounds from Tripterygium wilfordii Hook.f by electrospray ionization tandem mass spectrometry

Triptophenolide and its related compounds from Tripterygium wilfordii Hook.f is a kind of diterpenoids which shows anti-inflammatory activity. To study the metabolites of triptophenolide related compounds, the fragmentation mechanisms of them were investigated by using negative electrospray tandem mass spectrometry. With the aid of high resolution of ESI–QTOF–MS/MS, the fragmentation mechanisms of six diterpenoid compounds were systematically investigated. The fragmentation behavior mainly depends on what substituent groups the benzyl C ring bears. If there is a hydroxyl group on the position of C14, loss of CH 4 is dominating. However, the successive loss of two CH 3 radicals is predominant when the hydroxyl group of O14 is methylated. The lactone ring is prone to be dissociated to loss of CO, CO 2 and C 2H 2O 2 molecules. The pericyclic reaction can occur on A ring if there is an active hydrogen resides on C ring. Furthermore, one metabolite of compound A1 was confirmed by cytochrome P450 in vitro and the structure was proposed by tandem mass experiment together with the fragmentation mechanisms of this type of compounds.

The effect of signal suppression and mobile phase composition on the simultaneous analysis of multiple classes of acidic/neutral pharmaceuticals and personal care products in surface water by solid-phase extraction and ultra performance liquid chromatography–negative electrospray tandem mass spectrometry

A new multi-residue method for the determination of 25 acidic/neutral pharmaceuticals (antibiotics, anti-inflammatory/analgesics, lipid regulating agents, diuretics, triazides, H2-receptor antagonists, cardiac glicozides and angiotensin II antagonists) and personal care products (sunscreen agents and preservatives) in surface water with the usage of a new technique: ultra performance liquid chromatography–negative electrospray tandem mass spectrometry (UPLC–MS/MS) was developed and validated. The novel UPLC system with 1.7 μm particle-packed column allowed for good resolution of analytes with the application of low mobile phase flow rates (0.05 mL min −1) and short retention times (from 4.7 min to 13.3 min) delivering a fast and cost-effective multi-residue method. SPE with the usage of Oasis MCX strong cation-exchange mixed-mode polymeric sorbent was chosen for sample clean-up and concentration. The influence of mobile-phase composition, matrix assisted ion suppression and SPE recovery on the sensitivity of the method was identified and quantified. The instrumental limits of quantification varied from 0.2 μg L −1 to 30 μg L −1. The method limits of quantification were at low nanogram per litre levels and ranged from 0.3 ng L −1 to 30 ng L −1. The instrumental and method intra-day and inter-day repeatabilities were on average less than 5%. The method was successfully applied for the determination of PPCPs in River Taff. Thirteen compounds were determined in river water at levels ranging from a single to a few hundred nanograms per litre. Among them were ten pharmaceuticals (aspirin, salicylic acid, ketoprofen, naproxen, diclofenac, ibuprofen, mefenamic acid, furosemide, sulfasalazine and valsartan) and three personal care products (methyl- and ethylparaben and 4-benzophenone).

High-throughput urine screening for Smith–Lemli–Opitz syndrome and cerebrotendinous xanthomatosis using negative electrospray tandem mass spectrometry

Background Smith–Lemli–Opitz syndrome (SLOS) and cerebrotendinous xanthomatosis (CTX) are disorders affecting cholesterol metabolism. Currently, diagnosis relies on clinical recognition and specific and complex biochemical testing. Methods A rapid, high-throughput urine test, suitable for mass screening for these two disorders, was developed using flow injection negative electrospray tandem mass spectrometry with multiple reaction monitoring. Cholestane-pentol glucuronide, a known marker for CTX, was measured and a steroid sulfate with a proposed keto-pregnadien-diol structure was identified and measured for SLOS. Measurement of the two markers was readily incorporated into an existing tandem mass spectrometry method for diagnosing inborn errors of amino and organic acid metabolism. Results Levels in affected patients were well separated from 1738 controls, ranging from 6.7 to 100 times the 99.7th percentile of controls in SLOS patients ( n = 3) and 7.3 to 24 times the 99.7th percentile of controls in CTX patients ( n = 4). Conclusions The addition of testing for SLOS and CTX to a routine tandem mass spectrometry urine screening program simplifies the diagnosis of these two disorders and further extends the range of inborn errors of metabolism detected by this technique.

Rapid Response of Arctic Ringed Seals to Changes in Perfluoroalkyl Production

Temporal trends in perfluoroalkyl compounds (PFCs) were investigated in liver samples from two ringed seal (Phoca hispida) populations in the Canadian Arctic, Arviat (Western Hudson Bay) (1992, 1998, 2004, 2005) and Resolute Bay (Lancaster Sound) (1972, 1993, 2000, 2004, 2005). PFCs analyzed included C7-C15 perfluorinated carboxylates (PFCAs) and their suspected precursors, the 8:2 and 10:2 fluorotelomer saturated and unsaturated carboxylates (FTCAs, FTUCAs), C4, C6, C8, C10 sulfonates, and perfluorooctane sulfonamide (PFOSA). Liver samples were homogenized, liquid-liquid extracted with methyl tert-butyl ether, cleaned up using hexafluoropropanol, and analyzed by liquid chromatography with negative electrospray tandem mass spectrometry (LC-MS/MS). C9-C15 PFCAs showed statistically significant increasing concentrations during 1992-2005 and during 1993-2005 at Arviat and Resolute Bay, respectively. Doubling times ranged from 19.4 to 15.8 years for perfluorododecanoate (PFDoA) to 10.0-7.7 years for perfluorononanoate (PFNA) at Arviat and Resolute Bay but were shorter when excluding the 2005 samples. Conversely, perfluorooctane sulfonate (PFOS) and PFOSA concentrations showed maximum concentrations during 1998 and 2000 at Arviat and Resolute Bay, with statistically significant decreases from 2000 to 2005. In the case of Arviat, two consecutive decreases were measured from 1998 to 2003 and from 2003 to 2005. PFOS disappearance half-lives for seals at Arviat and Resolute Bay were 3.2 and 4.6 years. These results indicate that the ringed seals and their food web are rapidly responding to the phase out of perfluorooctane sulfonyl fluoride based compounds by 3M in 2001. Further, the relatively short doubling times of the PFCAs and PFOS disappearance half-lives support the hypothesis of atmospheric transport as the main transport mechanism of PFCs to the arctic environment.

Simultaneous determination of losartan, EXP-3174 and hydrochlorothiazide in plasma via fully automated 96-well-format-based solid-phase extraction and liquid chromatography–negative electrospray tandem mass spectrometry

An automated, sensitive and high-throughput liquid chromatographic/electrospray tandem mass spectrometric (LC-MS/MS) assay was developed for the simultaneous determination of losartan (LOS), its major circulating metabolite EXP-3174 and hydrochlorothiazide (HCTZ) in human plasma. LOS and HCTZ coexist in the same drug formulation, and this is the first method that enables the simultaneous determination of both drugs along with the active metabolite of LOS. Since these drugs have different physicochemical properties, the employment of a liquid-liquid extraction (LLE) protocol was precluded. A fully automated solid-phase extraction (SPE) protocol, based on 96-well format plates, was used to isolate these compounds and furosemide (internal standard, IS) from plasma. Washing and elution steps were amended accordingly in order to minimize any matrix effect from components of the plasma without reducing the elution of the molecules of interest. The compounds were eluted from a C18 column and detected with an API 3000 triple-quadrupole mass spectrometer using negative electrospray ionization and multiple reaction monitoring (MRM). The assay was linear over the range 1.00-400 ng/mL for LOS and EXP-3174 and 0.500-200 ng/mL for HCTZ, respectively, when 200 microl of plasma was used in the extraction. The overall intra- and interassay variations were within acceptance limits. The analysis time for each sample was 4 min, and more than 300 samples could be analyzed in one day by running the system overnight. The assay was simple, highly sensitive, selective, precise, fast, and it enables the reliable determination of LOS, EXP-3174 and HCTZ in pharmacokinetic or bioequivalence studies after per os administration of a single tablet containing both drugs.

Analysis of silymarin extracted from a commercial dosage by combining liquid‐liquid extraction with negative electrospray tandem mass spectrometry

Rapid Communications in Mass SpectrometryVolume 18, Issue 23 p. 2960-2962 Letter to the Editor Analysis of silymarin extracted from a commercial dosage by combining liquid-liquid extraction with negative electrospray tandem mass spectrometry Nadeem Ahmad Khan, Nadeem Ahmad Khan Department of Chemistry, Tamkang University, Tamsui, Taipei Hsien, 251, TaiwanSearch for more papers by this authorHui-Fen Wu, Corresponding Author Hui-Fen Wu [email protected] Department of Chemistry, Tamkang University, Tamsui, Taipei Hsien, 251, Taiwan Graduate Institute of Life Sciences, Tamkang University, Tamsui, Taipei Hsien, 251, TaiwanDepartment of Chemistry, Tamkang University, Tamsui, Taipei Hsien, 251, Taiwan.Search for more papers by this author Nadeem Ahmad Khan, Nadeem Ahmad Khan Department of Chemistry, Tamkang University, Tamsui, Taipei Hsien, 251, TaiwanSearch for more papers by this authorHui-Fen Wu, Corresponding Author Hui-Fen Wu [email protected] Department of Chemistry, Tamkang University, Tamsui, Taipei Hsien, 251, Taiwan Graduate Institute of Life Sciences, Tamkang University, Tamsui, Taipei Hsien, 251, TaiwanDepartment of Chemistry, Tamkang University, Tamsui, Taipei Hsien, 251, Taiwan.Search for more papers by this author First published: 04 November 2004 https://doi.org/10.1002/rcm.1700Citations: 15Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Citing Literature Volume18, Issue2315 December 2004Pages 2960-2962 RelatedInformation

Determination of the GABA B receptor agonist CGP 44532 (3-amino-2-hydroxypropylmethylphosphinic acid) in rat plasma after pre-column derivatization by micro-high-performance liquid chromatography combined with negative electrospray tandem mass spectrometry

An assay, based on pre-column derivatization and micro-high-performance liquid chromatography–tandem mass spectrometry, was developed for the determination of the GABA B agonist CGP 44532 in rat plasma. CGP 44532, a highly polar 3-amino-2( S)-hydroxypropylmethylphosphinic acid, presented difficulties in developing a chromatographic method for the analysis of the compound in rat plasma. Instead of analyzing the target compound directly, it was derivatized prior to separation to a 4-nitrobenzylcarbamate isopropyliden derivative. In order to reach the required quantitation limit, on-line solid-phase extraction was utilized for sample clean-up and reversed-phase micro-column high-performance liquid chromatography, for separation of the plasma samples. The separated compounds were detected by negative electrospray tandem mass spectrometry in selected reaction monitoring mode. The derivatives show good chromatographic and mass spectrometric properties and both the target compound and the internal standard, could be eluted as symmetrical peaks with good signal/noise ratio. The MS–MS detection was selective and sensitive due to the straight fragmentation pattern. After injection of 200-μl sample aliquots, the limit of quantification was 10 ng ml −1. The analytical assay is useable in the range of 10–500 ng ml −1.

Quantitation of Cyclic Nucleotides in Biological Samples by Negative Electrospray Tandem Mass Spectrometry Coupled to Ion Suppression Liquid Chromatography

Quantitation of Cyclic Nucleotides in Biological Samples by Negative Electrospray Tandem Mass Spectrometry Coupled to Ion Suppression Liquid Chromatography

Quantitation of Cyclic Nucleotides in Biological Samples by Negative Electrospray Tandem Mass Spectrometry Coupled to Ion Suppression Liquid Chromatography

Measurement of cyclic nucleotides by electrospray ionization mass spectrometry constitutes an unequivocal quantitative and qualitative technique superior to the established estimation methods of UV spectroscopy, radioimmunoassay (RIA), enzyme-linked immunosorbent assay (ELISA) and other mass spectrometric ionization techniques such as electron impact, thermospray and fast-atom bombardment. Optimal conditions for negative-ion electrospray tandem mass spectrometry showed a linear detection range using solutions with a concentration ranging from 10−6 and 5×10−9 M with an absolute detection limit of 100 fmol injected. Measurement of diagnostic product ions derived from low-energy collision-activated dissociation of the [M−H]− ions provided unambiguous identification. Quantitation of cyclic nucleotides present in biological samples in the femtomole region, needed further purification using on-line ion suppression high-performance liquid chromatography in order to avoid reduced sensitivity caused by matrix quenching.