Simultaneous online SPE-LC-MS/MS quantification of six widely used synthetic progestins in human plasma |
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Authors: | Christina?Moser Daniela?Zoderer Gerhard?Luef Markus?Rauchenzauner Ludwig?Wildt Andrea?Griesmacher Email author" target="_blank">Christoph?SegerEmail author |
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Institution: | 1.Division of Mass Spectrometry and Chromatography, Institute of Medical and Chemical Laboratory Diagnostics (ZIMCL),University Hospital Innsbruck,Innsbruck,Austria;2.Clinics for Neurology,University of Innsbruck, Medical School,Innsbruck,Austria;3.Department of Pediatrics,Saint Vincent Hospital Zams,Zams,Austria;4.Department of Pediatrics IV,Medical University Innsbruck,Innsbruck,Austria;5.Department of Gynecologic Endocrinology and Reproductive Medicine,Medical University of Innsbruck,Innsbruck,Austria |
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Abstract: | Co-administration of synthetic progestin containing hormonal contraceptives (HCs) and antiepileptic drugs (AEDs) is a common
clinical situation which needs specific considerations due to drug interactions. Several studies have demonstrated that lamotrigine
plasma levels are significantly decreased during co-medication with HCs, and that this interaction is associated with increased
seizure frequency in most of the cases. Additionally, an increase in contraceptive failure and unintended pregnancy could
be observed during co-medication. Hence, monitoring of progestin plasma levels in patients with AED co-medication is of interest.
A rapid and reliable online solid-phase extraction-high performance liquid chromatography–tandem mass spectrometry (online
SPE-LC-MS/MS) method using gradient elution in the LC domain was established and validated for the simultaneous quantitative
determination of gestodene, dienogest, drospirenone, etonogestrel, cyproterone acetate, and levonorgestrel in human plasma.
The online SPE-LC-MS/MS method covered a quantification concentration range of 5–100 ng/ml for dienogest, 1–100 ng/ml for
etonogestrel and 2–100 ng/ml for all other analytes. Stable isotope-labeled internal standards were used for analyte quantification
based on selected reaction monitoring experiments. Inter- and intra-assay precision and accuracy were determined from quality
control (QC) samples at the lower limits of quantification and at low, medium, and high concentration levels within the calibration
range. Inter-assay reproducibility at the QC levels was better than 10% (relative standard deviation, RSD), accuracy at these
levels ranged from −3.7% to 11.3%. Total extraction efficiency, tested at three concentrations, ranged from 92.5% to 106.4%.
Matrix interferences were excluded by post-column infusion experiments. To prove the applicability of the assay in clinical
cohorts, a sample set (n = 298) stemming from study patients under AED/oral HC co-medication was screened for progestin plasma levels. This method
has to be considered a research-use-only assay and must not be used for diagnostic or therapeutic purposes, since it did not
undergo formal performance evaluation in the sense of the IVD directive (98/79/EG) of the European Community. |
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