Excretion study of clomiphene in human urine: evaluation of endogenous steroids profile after multiple oral doses

Brito, Dayamín Martínez; Porto, Rodny Montes de Oca; Vidal, Margarita Teresa Correa; Ojeda, Roberto Socarrás; Pérez, Arístides Rosado

doi:10.1590/s0103-50532010001200008

Cited by 7 publications

(2 citation statements)

References 11 publications

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“…The influence of the administration of aromatase inhibitors on the parameters of the steroidal module of the ABP has been studied by various research groups . One of them described the influence of oral and multiple doses of tamoxifene, toremifene and clomifene and the conclusions were that, of the endogenous profile parameters of the ABP, only the T and E urinary concentrations increased significantly in males, generally after the second dose, while no significant variations were measured for the urinary concentrations of A, Etio, 5αAdiol and 5βAdiol and the ratios T/E, A/Etio and 5α/5β‐Adiols .…”

Section: Resultsmentioning

confidence: 99%

“…For that reason, proposed as good markers were the ratios A/Σ estrogens and Et/Σ estrogens. A study of 41 female and male Chinese subjects was performed by administering aminoglutetimide, anastrazol and letrozol, and it was also concluded that there was no common trend among the ABP biomarkers and the best markers were those related to estrogens …”

Section: Resultsmentioning

confidence: 99%

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Detection of urinary metabolites of arimistane in humans by gas chromatography coupled to high‐accuracy mass spectrometry for antidoping analyses

Brito

Torre

Botrè

2019

Rapid Comm Mass Spectrometry

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Rationale The selection of the most appropriate metabolites of the substances included in the Prohibited List of the World Anti‐Doping Agency (WADA) is fundamental for setting up methods allowing the detection of their intake by mass spectrometric methods. The aim of this work is to investigate the metabolism of arimistane (an aromatase inhibitor included in the WADA list) in order to improve its detection capacity among the antidoping community. Methods Urinary samples collected after controlled single administration of arimistane in three healthy volunteers were analysed using the common routine sample preparation in antidoping laboratories to determine the steroid profile parameters considered in the steroid module of the Athlete Biological Passport by gas chromatography coupled to tandem mass spectrometry (GC/MS/MS). For the elucidation of the proposed metabolites, GC coupled to high‐accuracy MS (GC/qTOFMS) was used. Both mass spectrometers were operated in electron ionization mode. Non‐conjugated (free), glucuronated and sulfated fractions were analysed separately. Results No relevant effects on the steroid profile could be detected after a single oral dose (25 mg). Up to 15 metabolites, present only in the post‐administration samples, were detected and some structures were postulated. These metabolites are mainly excreted as glucuro‐conjugated into urine and only minor amounts of two metabolites are also excreted unconjugated or as sulfates. Conclusions Arimistane itself was not observed in the free or glucuronated fractions, but only in the sulfate fraction. The peaks showing mass spectra in agreement with hydroxylated metabolites did not match with those for 7‐keto‐DHEA, 7α‐ or 7β‐hydroxy‐DHEA. This suggests that the first hydroxylation did not occur on C3, but on C2. These newly described metabolites allow the specific detection of arimistane misuse in sports.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Detection of urinary metabolites of arimistane in humans by gas chromatography coupled to high‐accuracy mass spectrometry for antidoping analyses

Brito

Torre

Botrè

2019

Rapid Comm Mass Spectrometry

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An in vitro assay approach to investigate the potential impact of different doping agents on the steroid profile

Piper

Heimbach

Adamczewski

et al. 2020

Drug Testing and Analysis

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The steroid profile, that is, the urinary concentrations and concentration ratios of selected steroids, is used in sports drug testing to detect the misuse of endogenous steroids such as testosterone. Since several years, not only population-based thresholds are applied but also the steroid profile is monitored via the Athlete Biological Passport whereby the individual reference ranges derived from multiple test results of the same athlete are compared to population-based thresholds. In order to maintain a high probative force of the passport, samples collected or analyzed under suboptimal conditions should not be included in the longitudinal review. This applies to biologically affected or degraded samples and to samples excluded owing to the presence of other substances potentially (or evidently) altering the steroid profile. Nineteen different doping agents comprising anabolic steroids, selective androgen receptor modulators, selective estrogen receptor modulators, ibutamoren, and tibolone were investigated for their effect on the steroid profile using an androgen receptor activation test, an androgen receptor binding assay, an aromatase assay, and a steroidogenesis assay. The in vitro tests were coupled with well-established liquid chromatography/mass spectrometry-based analytical approaches and for a subset of steroidal analytes by gas chromatography/mass spectrometry. The variety of tests employed should produce a comprehensive data set to better understand how a compound under investigation may impact the steroid profile. Although our data set may allow an estimate of whether or not a substance will have an impact on the overall steroid metabolism, predicting which parameter in particular may be influenced remains difficult.

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Quantification of clomiphene metabolite isomers in human plasma by rapid-resolution liquid chromatography–electrospray ionization–tandem mass spectrometry

et al. 2011

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Since the 1960s, clomiphene citrate is used for ovulation induction. Since nonresponse to clomiphene therapy is still not well understood, interindividual variability of clomiphene metabolism has been considered to be a plausible explanation. Therefore, a comprehensive, rapid, sensitive, and specific analytical method for the quantification of (E)- and (Z)-isomers of clomiphene and their putative N-desethyl, N,N-didesethyl, 4-hydroxy, and 4-hydroxy-N-desethyl metabolites, and the N-oxides in human plasma has been newly developed, using HPLC-tandem mass spectrometry and stable isotope-labeled internal standards. All standards other than the parent drug were synthesized in our laboratory. Following protein precipitation analytes were separated on a ZORBAX Eclipse plus C18 1.8 μm column with a gradient of 0.1% formic acid in water and 0.1% formic acid in acetonitrile and detected on a triple quadrupole mass spectrometer with positive electrospray ionization in the multiple reaction monitoring mode. Lower limit of quantification for metabolites ranged from 0.06 ng/mL for clomiphene-N-oxides to 0.3 ng/mL for (E)-N-desethylclomiphene. The assay was validated according to FDA guidelines. Plasma levels of clomiphene and its metabolites were measured in two women after single-dose treatment with clomiphene.

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Excretion study of clomiphene in human urine: evaluation of endogenous steroids profile after multiple oral doses

Cited by 7 publications

References 11 publications

Detection of urinary metabolites of arimistane in humans by gas chromatography coupled to high‐accuracy mass spectrometry for antidoping analyses

Detection of urinary metabolites of arimistane in humans by gas chromatography coupled to high‐accuracy mass spectrometry for antidoping analyses

An in vitro assay approach to investigate the potential impact of different doping agents on the steroid profile

Quantification of clomiphene metabolite isomers in human plasma by rapid-resolution liquid chromatography–electrospray ionization–tandem mass spectrometry

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