title: Androgen glucuronides analysis by liquid chromatography tandem-mass spectrometry: could it raise new perspectives in the diagnostic field of hormone-dependent malignancies?
abstract: Breast and prostate constitute organs of intense steroidogenic activity. Clinical and epidemiologic data provide strong evidence on the influence of androgens and estrogens on the risk of typical hormone-dependent malignancies, like breast and prostate cancer. Recent studies have focused on the role of androgen metabolites in regulating androgen concentrations in hormone-sensitive tissues. Steroid glucuronidation has been suggested to have a prominent role in controlling the levels and the biological activity of unconjugated androgens. It is well-established that serum levels of androgen glucuronides reflect androgen metabolism in androgen-sensitive tissues. Quantitative analysis of androgen metabolites in blood specimens is the only minimally invasive approach permitting an accurate estimate of the total pool of androgens. During the past years, androgen glucuronides analysis most often involved radioimmunoassays (RIA) or direct immunoassays, both methods bearing serious limitations. However, recent impressive technical advances in mass spectrometry, and particularly in high performance liquid chromatography coupled with mass spectrometry (LC-MS/MS), have overcome these drawbacks enabling the simultaneous, quantitative analysis of multiple steroids even at low concentrations. Blood androgen profiling by LC-MS/MS, a robust and reliable technique of high selectivity, sensitivity, specificity, precision and accuracy emerges as a promising new approach in the study of human pathology. The present review offers a contemporary insight in androgen glucuronides profiling through the application of LC-MS/MS, highlighting new perspectives in the study of steroids and their implication in hormone-dependent malignancies.
authors.affiliation: Research Center, Hellenic Anticancer Institute, Athens, Greece.
authors.forename: Eleni
authors.initials: E
authors.lastname: Kalogera
authors.forename: Constantinos
authors.initials: C
authors.lastname: Pistos
authors.forename: Xeni
authors.initials: X
authors.lastname: Provatopoulou
authors.forename: Sotirios
authors.initials: S
authors.lastname: Athanaselis
authors.forename: Chara
authors.initials: C
authors.lastname: Spiliopoulou
authors.forename: Antonia
authors.initials: A
authors.lastname: Gounaris
mesh_terms: D000728:Androgens / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D002853:Chromatography, Liquid / Q000379:methods*; D020719:Glucuronides / Q000032:analysis*; D006801:Humans; D009376:Neoplasms, Hormone-Dependent / Q000737:chemistry* / Q000175:diagnosis; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000728:Androgens; D014408:Biomarkers, Tumor; D020719:Glucuronides
keywords: 3α-diol; 3α-diol-17G; 3α-diol-3G; 3α-diol-G; 4-Dione; 4-androstenedione; 5α-androstane-3β, 17β-diol; A-diol; ADT; ADTG; APCI; APPI; Aanediol; Aenediol; Androgen glucuronides; DHEA; DHEAS; DHT; ER; ER-α; ESI; GC–MS; HSD; Hormone-dependent malignancies; IS; LC–MS; LC–MS/MS; LLE; LLOQ; Liquid chromatography; MRM; Mass spectrometry; QTrap; Quantitative analysis; RIA; Review; SHBG; SPE; T; UDPGA; UHPLC-QTOF-MS; androst-5-ene-3β, 17β-diol; androstane-3α, 17β-diol; androstane-3α, 17β-diol-17-glucuronide; androstane-3α, 17β-diol-3-glucuronide; androstane-3α, 17β-diol-glucuronide; androstene-3β, 17β-diol; androsterone; androsterone glucuronide; atmospheric pressure chemical ionization; atmospheric pressure photo ionization; dehydroepiandrosterone; dehydroepindrosterone sulfate; dihydrotestosterone; electrospray ionization interface; estrogen receptor-α; estrogenic receptor; gas chromatography–mass spectrometry; hybrid linear ion trap-triple quadrupole mass spectrometer; hydroxysteroid dehydrogenase; internal standard; liquid chromatography–mass spectrometry; liquid chromatography–tandem mass spectrometry; liquid–liquid extraction; lower limit of quantification; multiple reaction monitoring; radioimmunoassay; sex hormone-binding globulin; solid phase extraction; testosterone; ultra-high pressure liquid chromatography quadrupole time-of-flight mass spectrometer; uridine-5′-diphosphoglucuronic acid