Simultaneous Measurement of Cortisol, Cortisone, Dexamethasone and Additional Exogenous Corticosteroids by Rapid and Sensitive LC–MS/MS Analysis

The simultaneous measurement of dexamethasone and cortisol has proven the ability to increase the diagnostic performance of the overnight dexamethasone-suppression test. Furthermore, the therapeutic drug monitoring of administered corticosteroid drugs could represent a crucial tool for investigating unexpected variations of steroid hormones’ circulating levels. In this work, an LC–MS/MS method for the quantification of cortisol, cortisone, dexamethasone and six additional exogenous corticosteroids in the serum/plasma matrix was developed and validated in compliance with the ISO/IEC requirements. To assess the efficiency of the validated method, serum samples of 75 patients undergoing the dexamethasone-suppression test and 21 plasma samples of patients under immunosuppressive treatment after kidney transplant were analyzed. In all dexamethasone-suppression test samples, it was possible to measure the circulating levels of cortisol, cortisone and dexamethasone. Concentrations of the latter were for all tested patients above the proposed cutoff for the dexamethasone-suppression test’s results, and the cortisol concentrations showed good correlation with the ones measured by routine immunometric analysis, therefore confirming the screening outcome for all enrolled patients. Prednisone was detected and quantified in all enrolled patients, confirming the use of such a corticosteroid for immunosuppressive therapy. Thanks to these two applications, we proved the overall performance of the developed LC–MS/MS method for four target analytes. The future implementation of such an analytical tool in the clinical biochemistry laboratory’s routine will guarantee a single and versatile tool for simultaneously monitoring dexamethasone-suppression-test results and corticosteroid drugs’ administration

Total Value of Ownership and Overall Equipment Effectiveness analysis to evaluate the impact of automation on time and costs of therapeutic drug monitoring

Abstract Total Value of Ownership (TVO) and Overall Equipment Effectiveness (OEE) analysis are novel tools capable of monitoring and analyzing industrial processes by assessing the efficiency of the entire instrumental equipment and calculating instrument capacity utilization. Such integrated analysis, measuring quality indicators of the testing process, could also provide new perspectives and methodologies for the workflow organization of clinical laboratories. In this study, TVO and OEE were employed for the evaluation of two different configurations of a therapeutic drug monitoring sector, comparing the results obtained for immunosuppressant (ISD) and anti-epileptic drugs (AED) analysis as well as checking their quantitative performance in terms of limit of quantification, accuracy and precision. TVO analysis was performed for ISDs, including the Total Direct Labor Time, Total Cycle Time and Turnaround Time as well as cost of testing. Instruments' performance and workload were assessed using OEE indicator, studying Availability, Performance and Quality factors. Total Cycle Time for a batch was 3.55 h, decreasing of 1.5 h in the new setting where personnel are engaged for 0.98 h, 25% of total testing time. The calculated cost per sample was 6.60 euro. Availability values were significantly higher for automated sample-handling system and ISDs analysis by LC-MS. Higher Performance values were obtained for LC-MS system for AED and other TDM. Quality values were >0.94 for all instruments. TVO and OEE proved to be applicable to clinical laboratory environment, quantifying benefits and costs of newly developed semi-automated therapeutic drug monitoring sector. This novel approach based on an integrated analysis may help activity planning and quality improvement and could be used in the future for benchmarking progress as a product/process comparison tool in other laboratory fields