A web application to support the coordination of reflexive, interpretative toxicology testing.

Background: Reflexive laboratory testing workflows can improve the assessment of patients receiving pain medications chronically, but complex workflows requiring pathologist input and interpretation may not be well-supported by traditional laboratory information systems. In this work, we describe the development of a web application that improves the efficiency of pathologists and laboratory staff in delivering actionable toxicology results. Method: Before designing the application, we set out to understand the entire workflow including the laboratory workflow and pathologist review. Additionally, we gathered requirements and specifications from stakeholders. Finally, to assess the performance of the implementation of the application, we surveyed stakeholders and documented the approximate amount of time that is required in each step of the workflow. Results: A web-based application was chosen for the ease of access for users. Relevant clinical data was routinely received and displayed in the application. The workflows in the laboratory and during the interpretation process served as the basis of the user interface. With the addition of auto-filing software, the return on investment was significant. The laboratory saved the equivalent of one full-time employee in time by automating file management and result entry. Discussion: Implementation of a purpose-built application to support reflex and interpretation workflows in a clinical pathology practice has led to a significant improvement in laboratory efficiency. Custom- and purpose-built applications can help reduce staff burnout, reduce transcription errors, and allow staff to focus on more critical issues around quality.

Listening to your mass spectrometer: An open-source toolkit to visualize mass spectrometer data.

INTRODUCTION: We have developed a set of tools built with open-source software that includes both a database and a visualization component to collect LC-MS/MS data and monitor quality control parameters. DESCRIPTION OF TOOL: To display LC-MS/MS data we built a parsing tool using Python and standard libraries to parse the XML files after each clinical run. The tool parses the necessary information to store a database comprised of three distinct tables. Another component to this toolkit is an interactive data visualization tool that uses the data from the database. There are 5 different visualizations that present the data based on interchangeable parameters. EVALUATION OF TOOL: Using histogram visualization, we assessed how quality control parameters that feed our quality control algorithm, SMACK, which assists to improve the efficiency of data review and results, performed against the collective data. Using the newly identified QC parameter values from the toolkit, we compared the output of the SMACK algorithm; the number of QC flags changed in that there was a 1.7% (31/1944 observations) increase in flags and a 7.1% (138/1944 observations) decrease in presumed false positive flags, increasing the overall performance of SMACK which helped staff focus their time on reviewing more concerning QC failures. DISCUSSION: We have developed a customizable web-based dashboard for instrument performance monitoring for our opiate confirmation LC-MS/MS assay using data collected with each batch. The web-based platform allows users to monitor instrument performance and can encompass other instruments throughout the laboratory. This information can help the laboratory take proactive measures to maintain instruments, ultimately reducing the amount down time needed for maintenance.

Analysis of Busulfan in Plasma by Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS).

Bone marrow transplantation is used to treat particular types of cancers such as lymphoma, leukemia, and multiple myeloma. Appropriate dosing of busulfan during the preparative phase is critical for a successful allograft; if blood concentrations get too high significant liver toxicity can occur, if blood concentrations are too low, then graft-versus-host disease (GVHD) can develop. Busulfan monitoring in blood allows hospitals with the opportunity to provide individualized medicine to patients and improve overall patient outcome. Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) is an important analytical method for quantification of busulfan in plasma in order to optimize the dose. © 2020 Wiley Periodicals LLC. Basic Protocol: Analysis of busulfan by liquid chromatography/mass spectrometry.

Analysis of Immunosuppressant Drugs in Whole Blood by Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS).

Immunosuppressant medications help suppress the immune system response through inhibition of various checkpoints in the regulatory biochemical pathway. This is useful in prevention of organ rejection in transplantation or in the treatment of autoimmune diseases such as lupus or rheumatoid arthritis. Quantification of immunosuppressive drugs in blood is needed clinically for optimization of treatment and to avoid toxicity or unwanted side effects. Here, we describe a quantitative method to determine the concentration of cyclosprine A, tacrolimus, sirolimus, and everolimus in whole blood. This method has been used for many years clinically to support patient care. © 2020 by John Wiley & Sons, Inc.

Automated analysis of dried urine spot (DUS) samples for toxicology screening.

BACKGROUND: Dried specimens have been proposed in multiple environments to minimize costs associated with specimen storage and shipping in clinical studies. This report describes the development and validation of an automated method for qualitative toxicology screening of dried urine samples using LC-MS/MS. METHODS: Urine standards containing 41 compounds were prepared and applied to filter paper cards. Dried urine was eluted from the cards using a Dried Blood Spot (DBS) autosampler from Spark Holland, which was plumbed inline with a Thermo Scientific Turboflow chromatography system for subsequent MS/MS detection with selected reaction monitoring. Limits of detection, precision of peak areas, repeatability, and carryover studies were conducted. Concordance with a reference LC-MS/MS method using liquid samples was evaluated using remnant discarded specimens. RESULTS: The limit of detection ranged from 5 to 75 ng/mL for most compounds. At the LOD for each analyte, the peak area precision ranged from 8 to 29%. For 20 repeat injections of samples spiked at ±25% of the LOD, there was a 4% false positive rate for the 75% × LOD samples, and a 0.4% false negative rate for the +125% × LOD samples. In comparing 40 known positive specimens analyzed with the DUS method and a liquid urine reference method, there was 88% agreement. Analysis of 10 known negative specimens yielded negative results. There was no significant carryover detected up to 2000 ng/mL for any of the analytes in the assay. CONCLUSION: Using a robotic DUS sampling an inline HTLC-MS/MS system, we have developed and validated a fully-automated and robust method for multi-analyte detection of drugs of abuse in dried urine specimens.