Determination of exemestane and 17-hydroxyexemestane by high-performance liquid chromatography coupled with tandem mass spectrometry and high-resolution mass spectrometry

Semenistaya, E. N.; Dikunets, M. A.; Viryus, E. D.; Rodchenkov, G. M.

doi:10.1134/s1061934810050114

Cited by 7 publications

(2 citation statements)

References 6 publications

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“…In addition, the quantification limits for EXE, DHE and DHE-Gluc were 3 nM, 1.8 nM and 1.5 nM, respectively, in plasma, and 0.9 nM, 3 nM and 15 nM, respectively, in urine. These limits are comparable to those observed in previous studies, where the lower limits of quantification were 0.2 ng/mL and 0.1 ng/mL for EXE and 17β-DHE, respectively, in plasma and the lower limits of detection were 1 ng/mL for both in urine ( 39 , 40 ). Of the ninety-six subjects analyzed in the present study, all exhibited detectable EXE, 17β-DHE or 17β-DHE-Gluc in plasma with only 4 exhibiting levels that were below the detection limit for EXE, 17β-DHE and 17β-DHE-Gluc in urine.…”

Section: Discussionsupporting

confidence: 89%

Role of the UGT2B17 deletion in exemestane pharmacogenetics

et al. 2017

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Exemestane (EXE) is an aromatase inhibitor used for the prevention and treatment of breast cancer. The major metabolic pathway for EXE is reduction to form the active 17β-dihydro-EXE (17β-DHE) and subsequent glucuronidation to 17β-hydroxy-EXE-17-O-β-D-glucuronide (17β-DHE-Gluc) by UGT2B17. The aim of the present study was to determine the effects of UGT2B17 copy number variation on the levels of urinary and plasma 17β-DHE-Gluc and 17β-DHE in patients taking EXE. Ninety-six post-menopausal Caucasian breast cancer patients with ER+ breast tumors taking 25 mg EXE daily were recruited into this study. UGT2B17 copy number was determined by a real-time PCR copy number variant assay and the levels of EXE, 17β-DHE and 17β-DHE-Gluc were quantified by UPLC/MS in patients’ urine and plasma. A 39-fold decrease (P<0.0001) in the levels of creatinine-adjusted urinary 17β-DHE-Gluc was observed among UGT2B17 (*2/*2) subjects vs. subjects with the UGT2B17 (*1/*1) genotype. The plasma levels of 17β-DHE-Gluc was decreased 29-fold (P<0.0001) in subjects with the UGT2B17 (*2/*2) genotype vs. subjects with UGT2B17 (*1/*1) genotype. The levels of plasma EXE-adjusted 17β-DHE was 28% higher (P=0.04) in subjects with the UGT2B17 (*2/*2) genotype vs. subjects with the UGT2B17 (*1/*1) genotype. These data indicate that UGT2B17 is the major enzyme responsible for 17β-DHE-Gluc formation in vivo and that the UGT2B17 copy number variant may play a role in inter-individual variability in 17β-DHE levels in vivo.

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Section: Discussionsupporting

confidence: 89%

Role of the UGT2B17 deletion in exemestane pharmacogenetics

et al. 2017

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“…Low detection limits (3 × 10 -13 -1.2 × 10 -12 g) have been achieved in real samples. [97][98][99][100][101] Researchers from ADC have developed an approach allowing the maximization of the number of compounds that can be determined with high sensitivity in a single run. 102 It involves so-called "wrong-way-round ionization" in ESI for the simultaneous detection of multiple classes of doping substances (stimulants, diuretics, b 2 -agonists, b-blockers, antiestrogens, glucocorticosteroids and anabolic agents) without the need to switch the polarity.…”

Section: Doping-controlmentioning

confidence: 99%

Mass Spectrometry in Russia

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2013

Eur J Mass Spectrom (Chichester)

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The present review covers the main research in the area of mass spectrometry from the 1990s which was about the same time as the Russian Federation emerged from the collapse of the Soviet Union (USSR). It consists of two main parts-application of mass spectrometry to chemistry and related fields and creation and development of mass spectrometric technique. Both traditional and comparatively new mass spectrometric methods were used to solve various problems in organic chemistry (reactivity of gas-phase ions, structure elucidation and problems of identification, quantitative and trace analysis, differentiation of stereoisomers, derivatization approaches etc.), biochemistry (proteomics and peptidomics, lipidomics), medical chemistry (mainly the search of biomarkers, pharmacology, doping control), environmental, petrochemistry, polymer chemistry, inorganic and physical chemistry, determination of natural isotope ratio etc. Although a lot of talented mass spectrometrists left Russia and moved abroad after the collapse of the Soviet Union, the vitality of the mass spectral community proved to be rather high, which allowed the continuation of new developments in the field of mass spectrometric instrumentation. They are devoted to improvements in traditional magnetic sector mass spectrometers and the development of new ion source types, to analysis and modification of quadrupole, time-of-flight (ToF) and ion cyclotron resonance (ICR) analyzers. The most important achievements are due to the creation of multi-reflecting ToF mass analyzers. Special attention was paid to the construction of compact mass spectrometers, particularly for space exploration, of combined instruments, such as ion mobility spectrometer/mass spectrometer and accelerating mass spectrometers. The comparatively young Russian Mass Spectrometry Society is working hard to consolidate the mass spectrometrists from Russia and foreign countries, to train young professionals on new appliances and regularly holds conferences on mass spectrometry. For ten years, a special journal Mass-spektrometria has published papers on all disciplines of mass spectrometry.

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Current literature in mass spectrometry

2010

J. Mass Spectrom.

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Determination of exemestane and 17-hydroxyexemestane by high-performance liquid chromatography coupled with tandem mass spectrometry and high-resolution mass spectrometry

Cited by 7 publications

References 6 publications

Role of the UGT2B17 deletion in exemestane pharmacogenetics

Role of the UGT2B17 deletion in exemestane pharmacogenetics

Mass Spectrometry in Russia

Current literature in mass spectrometry

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