ArticleTherapeutic drug monitoring2026
Simultaneous Quantification of Dexamethasone and Cortisol for the Dexamethasone Suppression Test Using LC-MS/MS: Adaptation of a Commercial CE-IVD Steroid Assay.
Article in Therapeutic drug monitoring, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundThe dexamethasone suppression test (DST) is a key diagnostic tool for evaluating disorders of the hypothalamic-pituitary-adrenal (HPA) axis. Interpretation of DST results can be confounded by inadequate dexamethasone exposure due to pharmacokinetic variability or patient nonadherence. Simultaneous measurement of dexamethasone and cortisol by LC-MS/MS improves diagnostic accuracy by distinguishing true biological nonsuppression from insufficient drug exposure and prevents analytical interferences observed with cortisol immunoassays.
methodsA commercially available CE-IVD LC-MS/MS steroid panel (Chromsystems) was adapted for the simultaneous quantification of dexamethasone and cortisol in human plasma. The method was validated for linearity, accuracy, precision, selectivity, carry-over, matrix effects, and stability. Method comparison was performed using 26 clinical DST samples analyzed using immunoassay and external LC-MS testing. The proposed dexamethasone cutoff of 1.3 ng/mL (3.3 nmol/L) was evaluated in 62 patient samples.
resultsThe method demonstrated excellent linearity, with intra- and interassay accuracy and precision within ±15% for both analytes. No relevant carry-over or matrix effects were observed. Agreement with reference methods was 91% ± 6% for cortisol and 95% ± 7% for dexamethasone. Among the 62 DST samples, 48 showed appropriate suppression [cortisol <18.12 ng/mL (<50 nmol/L)] with dexamethasone levels above the cutoff. In contrast, 3 samples with insufficient suppression [cortisol >48.6 ng/mL (134.1 nmol/L)] had subthreshold dexamethasone levels, whereas 11 samples showed elevated cortisol levels despite sufficient dexamethasone exposure, indicating possible HPA axis dysfunction.
conclusionsThe proposed rapid and robust LC-MS/MS method enables reliable, simultaneous quantification of dexamethasone and cortisol. The assay supports accurate DST interpretation by identifying cases of pharmacokinetic variance or nonadherence.
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