Analysis of a Challenging Subset of World Anti-Doping Agency-Banned Steroids and Antiestrogens by LC-MS-MS

Borges, Chad R.; Miller, Nicole L.; Shelby, Melinda K.; Hansen, Megan; White, Claudia; Slawson, Matthew H.; Monti, Kim M.; Crouch, Dennis J.

doi:10.1093/jat/31.3.125

Cited by 29 publications

(14 citation statements)

References 7 publications

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“…Over the years chemical derivatization techniques have been developed to enhance the ionization of various analytes in LC-MS [11][12][13][14]. The deficiency of poor ionization of steroids in LC-MS has now been largely overcome; a number of derivatization procedures that involve either the introduction of a group carrying a formal charge [15][16][17][18] or the attachment of a group with high proton affinity [14,[19][20][21][22] are now used to enhance ionization efficiency for positive ion detection in steroid analysis by LC-MS and LC-MS/MS.…”

Section: Introductionmentioning

confidence: 99%

Analysis of steroidal estrogens as pyridine-3-sulfonyl derivatives by liquid chromatography electrospray tandem mass spectrometry

Spink

2008

Analytical Biochemistry

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Sulfonyl chlorides substituted with functional groups having high proton affinity can serve as derivatization reagents to enhance the sensitivity for steroidal estrogens in liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). The most commonly used reagent for derivatization of estrogens for LC-ESI-MS/MS is dansyl chloride. In this study, we compared dansyl chloride, 1,2-dimethylimidazole-4-sulfonyl (DMIS) chloride, pyridine-3-sulfonyl (PS) chloride, and 4-(1H-pyrazol-1-yl)benzenesulfonyl (PBS) chloride for derivatization of 17β-estradiol (E2) prior to LC-ESI-MS/MS. The product ion spectra of the dansyl and DMIS derivatives were dominated by ions representing derivatization reagent moieties. In contrast, the product ion spectrum of the PS derivative of E2 and, to a lesser extent, the PBS derivative, showed analytespecific fragment ions. Derivatization with PS chloride was therefore chosen for further investigation. The product ion spectrum of the PS derivative of E2 showed intense ions at m/z 272, assigned to the radical E2 cation, and at m/z 350, attributed to the loss of SO 2 from the [M+H] + ion. Third-stage mass spectrometry of the PS derivative of E2 with isolation and collisional activation of the m/z 272 ion resulted in steroid C and D ring cleavages analogous to those observed in electron ionization mass spectrometry. The product ion spectra of the PS derivatives of estrone, 17α-ethinylestradiol, equilin, and equilenin showed similar estrogen-specific ions. Using derivatization with PS chloride, we developed an LC-ESI-MS/MS method with multiple reaction monitoring of primary and confirmatory precursor-to-product ion transitions for the determination of E2 in serum.

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Section: Introductionmentioning

confidence: 99%

Analysis of steroidal estrogens as pyridine-3-sulfonyl derivatives by liquid chromatography electrospray tandem mass spectrometry

Spink

2008

Analytical Biochemistry

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“…LC/MS/MS is becoming more important in the analysis of anabolic steroids and metabolites. Recently, several LC/MS/MS methods have been published for multiresidue screening of these analytes5, 6 and a few methods based on precursor ion scanning have also been found useful for the detection of unknown (designer) steroids 7, 8…”

mentioning

confidence: 99%

Collision‐induced dissociation of 3‐keto anabolic steroids and related compounds after electrospray ionization. Considerations for structural elucidation

Pozo

Eenoo

Deventer

et al. 2008

Rapid Comm Mass Spectrometry

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The collision-induced dissociation of forty-one 3-keto anabolic steroids and related compounds has been studied using both triple quadrupole (QqQ) and hybrid quadrupole-time of flight (QTOF) instruments. Due to the complexity of the product ion spectra of these analytes, which generate a large number of ions, only two specific regions were studied in depth: the product ions near the precursor ion (m/z > or =M-100) and the most abundant product ions at a collision energy of 30 eV. Accurate mass measurements were used in order to obtain an unequivocal assignment of the empirical formula and the origin of each selected product ion. Analytes have been divided into eight groups according to the number and position of double bonds and the presence of functional groups such as hydroxyl- or nitrogen-containing rings. A correlation between the steroid structure and the product ions obtained has been postulated. The application of these correlations can be useful in the elucidation of feasible structures for unknown steroids and/or their metabolites.

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“…MS-based methods are powerful and very useful for use in sports doping laboratories because they are specific and sensitive detection methods. They, however, have the major limitation that they cannot identify compounds of unknown structure and rely on prior knowledge of the structure of the steroid (64,83–86). …”

Section: Biological Androgen Receptor Assaysmentioning

confidence: 99%

The Androgen Receptor and Its Use in Biological Assays: Looking Toward Effect-Based Testing and Its Applications

Cadwallader

Lim

Rollins

et al. 2011

Journal of Analytical Toxicology

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Steroid abuse is a growing problem among amateur and professional athletes. Because of an inundation of newly and illegally synthesized steroids with minor structural modifications and other designer steroid receptor modulators, there is a need to develop new methods of detection which do not require prior knowledge of the abused steroid structure. The number of designer steroids currently being abused is unknown because detection methods in general are only identifying substances with a known structure. The detection of doping is moving away from merely checking for exposure to prohibited substance toward detecting an effect of prohibited substances, as biological assays can do. Cell-based biological assays are the next generation of assays which should be utilized by antidoping laboratories; they can detect androgenic anabolic steroid and other human androgen receptor (hAR) ligand presence without knowledge of their structure and assess the relative biological activity of these compounds. This review summarizes the hAR and its action and discusses its relevance to sports doping and its use in biological assays.

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Analysis of a Challenging Subset of World Anti-Doping Agency-Banned Steroids and Antiestrogens by LC-MS-MS

Cited by 29 publications

References 7 publications

Analysis of steroidal estrogens as pyridine-3-sulfonyl derivatives by liquid chromatography electrospray tandem mass spectrometry

Analysis of steroidal estrogens as pyridine-3-sulfonyl derivatives by liquid chromatography electrospray tandem mass spectrometry

Collision‐induced dissociation of 3‐keto anabolic steroids and related compounds after electrospray ionization. Considerations for structural elucidation

The Androgen Receptor and Its Use in Biological Assays: Looking Toward Effect-Based Testing and Its Applications

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