A general screening method for doping agents in human urine by solid phase extraction and liquid chromatography/time-of-flight mass spectrometry

Kolmonen, Marjo; Leinonen, Antti; Pelander, Anna; Ojanperä, Ilkka

doi:10.1016/j.aca.2006.12.028

Cited by 153 publications

(96 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Thus, a key question is whether the medium mass resolving power provided by time-of-flight (TOF) instruments is sufficient to enable the detection and accurate mass measurement of residues at low ng/g level in complex sample matrices. The utility of full-scan LC-TOFMS for the comprehensive screening of urine samples for drugs [3,4] and doping agents [5], crops for pesticide residues [6], and confirmation of antibiotics and fungicides in salmon [7] was demonstrated. Comparison of theoretical and measured isotopic patterns might be a useful additional tool to accurate mass determination and facilitates the identification process [8].…”

mentioning

confidence: 99%

Full-scan accurate mass selectivity of ultra-performance liquid chromatography combined with time-of-flight and orbitrap mass spectrometry in hormone and veterinary drug residue analysis

Heeft¹,

Bolck²,

Beumer³

et al. 2009

J. Am. Soc. Mass Spectrom.

128

View full text Add to dashboard Cite

The applicability of ultra-performance liquid chromatography (UPLC) combined with fullscan accurate mass time-of-flight (TOF) and Orbitrap mass spectrometry (MS) to the analysis of hormone and veterinary drug residues was evaluated. Extracts from blank bovine hair were fortified with 14 steroid esters. UPLC-Orbitrap MS performed at a resolving power of 60,000 (FWHM) enabled the detection and accurate mass measurement (Ͻ3 ppm error) of all 14 steroid esters at low ng/g concentration level, despite the complex matrix background. A 5 ppm mass tolerance window proved to be essential to generate highly selective reconstructed ion chromatograms (RICs) having reduced background from the hair matrix. UPLC-Orbitrap MS at a lower resolving power of 7500 and UPLC-TOFMS at mass resolving power 10,000 failed both to detect all of the steroid esters in hair extracts owing to the inability to mass resolve analyte ions from co-eluting isobaric matrix compounds. In a second application, animal feed extracts were fortified with coccidiostats drugs at levels ranging from 240 to 1900 ng/g. UPLC-Orbitrap MS conducted at a resolving power of 7500 and 60,000 and UPLC-TOFMS detected all of the analytes at the lowest investigated level. Thanks to the higher analyte-to-matrix background ratio, the utilization of very narrow mass tolerance windows in the RIC was not required. This study demonstrates that even when the targeted sample preparation from conventional LC-MS/MS is applied to UPLC with full-scan accurate mass MS, false compliant (false negative) results can be obtained when the mass resolving power of the MS is insufficient to separate analyte ions from isobaric co-eluting sample matrix ions. The current trend towards more generic and less selective sample preparation is expected to aggravate this issue further. (J Am Soc Mass Spectrom 2009, 20, 451-463)

show abstract

mentioning

confidence: 99%

Full-scan accurate mass selectivity of ultra-performance liquid chromatography combined with time-of-flight and orbitrap mass spectrometry in hormone and veterinary drug residue analysis

Heeft¹,

Bolck²,

Beumer³

et al. 2009

J. Am. Soc. Mass Spectrom.

128

View full text Add to dashboard Cite

show abstract

“…L'excrétion urinaire d'un médicament et de ses métabolites correspond souvent à une fraction de la dose administrée. Seulement 2 % de la dose administrée de bromazépam se retrouve dans les urines sous forme inchangée, alors que le dérivé glucuronoconjugué du 3-hydroxybromazépam correspond à environ 27 % de la dose et que la somme des dérivés conjugués du produit de clivage et du produit de clivage hydroxylé correspondent environ à 40 % de la dose administrée (figure 6) [27,28].…”

Section: Discussionunclassified

“…Depuis maintenant quelques années, les couplages de systèmes chromatographiques avec des analyseurs mesurant la masse exacte se développent (temps de vol, orbitrap). Ils ouvrent de nouveaux champs d'investigation au toxicologue analyste [23][24][25][26][27][28]. Contrairement aux systèmes triple quadripolaire dont la limite de détection la plus basse est obtenue en mode dit MRM (Multi Reaction Monitoring), mode le plus sensible actuellement mais ne permettant de trouver que ce que l'on recherche et relativisant aussi grandement l'exhaustivité d'un criblage, l'acquisition en masse exacte a l'énorme avantage de se faire en mode dit « full scan » et non en mode ciblé.…”

Section: Introductionunclassified

Analyse toxicologique avec mesure par « masse exacte ». Caractérisation de métabolites urinaires par couplage UPLC/QTOF : apports et intérêts dans le cadre de la soumission chimique

Humbert¹,

Richeval²

2012

Ann Toxicol Anal

View full text Add to dashboard Cite

Résumé -Objectifs :Le métabolisme des médicaments conduit à des composés plus polaires facilitant leur élimi-nation dans les urines. Peu de médicaments sont retrouvés inchangés dans les urines. Souvent pour mettre en évidence une soumission chimique, le toxicologue reçoit du sang et des urines prélevés plusieurs jours voire une semaine après les faits. Plus les faits seront éloignés des prélèvements, plus les chances de mettre en évidence la moindre trace d'une substance s'amenuisent. Le but de ce travail a été de mettre en place un protocole permettant d'obtenir des informations spectrales sur des métabolites de psychotropes excrétés en grande quantité dans les urines. Méthodes : Les urines de patients ayant ingéré massivement un médicament sont analysées par chromatographie liquide couplée à un spectromètre de masse hybride quadripôle-temps de vol (UPLC XEVO G2 QTOF). Le mode MS e réalise une double acquisition simultanée : une à basse énergie d'accélération pour obtenir la masse exacte des composés, la seconde à haute énergie d'accélération pour fragmenter l'ensemble des composés. Les données sont traitées par des logiciels spécialisés dans la recherche et la caractérisation de métabolites (MetaboLynx TM ) et dans l'analyse des fragments de collision (MassFragment). Résultats : Dans les urines d'un patient ayant ingéré massivement du bromazépam, il a été possible de caractériser 3 métabolites majeurs. Lors d'une ingestion massive d'alimémazine, il a été possible de caractériser 5 métabolites majeurs. Conclusion : L'élargissement de la fenêtre de détection d'un composé dans des urines est possible par la caractérisation des métabolites. Mots clés : Soumission chimique, métabolites, masse exacteAbstract -Objective: The metabolism of drugs leads to more polar compounds, facilitating urinary elimination. Few drugs are recovered unchanged in the urine. Often, to highlight a chemical submission, the toxicologist receives blood and urine for events dating back to several days to a week. If the time between the events and the biological sample is long, the chance of highlighting a product is small. The aim of this study was to establish a protocol to obtain spectral information on metabolites of psychoactive drugs excreted in large quantities in the urine. Methods: The urines of patients who ingested a massive amount of a drug are analyzed by liquid chromatography-hybrid quadrupole timeof-flight mass spectrometry (UPLC QTOF XEVO G2). The MS e mode performs a double simultaneous acquisition: a low-energy acceleration to obtain the exact mass of compounds, the second at high acceleration energy to fragment all of the compounds. The data are processed by specialized software for research and characterization of metabolites (MetaboLynx TM ), and analysis of collision fragments (MassFragment). Results: In the urine of a patient who ingested a massive amount of bromazepam, it was possible to characterize three major metabolites. Also, after a massive ingestion of alimemazine it was possible to characterize five major metab...

show abstract

“…Sample extraction that cleans-up the sample matrix and concentrates trace amounts of the analyte are essential aspects of the analysis of biological sample. Traditional methods, such as liquid-liquid extraction (LLE) 9 and solid phase extraction (SPE), 10 are tedious, time-consuming and consume large amounts of solvent. Recently, new microextraction techniques such as solid phase microextraction (SPME), 11,12 and liquid phase microextraction (LPME) 13 have been developed because they are simple, fast and solvent-free or with less consumption of organic solvent.…”

Section: Introductionmentioning

confidence: 99%

Analysis of Matrine Alkaloids in Human Urine by Hollow Fiber Liquid-phase Microextraction with High-performance Liquid Chromatography

Han¹,

Row²

2010

Journal of the Korean Chemical Society

View full text Add to dashboard Cite

의 루멘에 pH 1.50의 100 mmol/L of H3PO4 수용체 용액을 주입한다, 1 mol/L NaOH는 공급 용액의 pH, 600 rpm의 교반속도와 60분의 추출시간을 조정하여 사용된다. LPME의 방법은 실제의 소변 샘플에서 마트린과 소포카르핌의 분석에 성공적으로 적용되었다. 주제어: 중공섬유 액상 미세추출, 인간 뇨, Matrine Alkaloids ABSTRACT.A sensitive quantitative method for the determination of matrine alkaloids in human urine was developed based on hollow fiber liquid-phase microextraction (HF-LPME) combined with HPLC. The influence of the different factors on the HF-LPME efficiency including the pH and ion strength of the donar solution, the pH of the acceptor solution, stirring rate and extraction time were examined. The best HF-LPME conditions were as follows: 1-octanol impregnated in the pores of the hollow fiber, 100 mmol/L of H3PO4 at pH 1.50 as the acceptor solution injected into the lumen of the hollow fiber, 1 mol/L NaOH used to adjust the pH of the donor solution, stirring rate of 600 rpm and extraction time of 60 min. The LPME method was applied successfully to the analysis of matrine and sophocarpine in real urine samples.

show abstract

A general screening method for doping agents in human urine by solid phase extraction and liquid chromatography/time-of-flight mass spectrometry

Cited by 153 publications

References 18 publications

Full-scan accurate mass selectivity of ultra-performance liquid chromatography combined with time-of-flight and orbitrap mass spectrometry in hormone and veterinary drug residue analysis

Full-scan accurate mass selectivity of ultra-performance liquid chromatography combined with time-of-flight and orbitrap mass spectrometry in hormone and veterinary drug residue analysis

Analyse toxicologique avec mesure par « masse exacte ». Caractérisation de métabolites urinaires par couplage UPLC/QTOF : apports et intérêts dans le cadre de la soumission chimique

Analysis of Matrine Alkaloids in Human Urine by Hollow Fiber Liquid-phase Microextraction with High-performance Liquid Chromatography

Contact Info

Product

Resources

About