MSACL 2018 US Abstract

Topic: Practical Training

Method Development Case History Part 1: Development and Validation

Stephanie Marin (Presenter)
Biotage

Bio: Stephanie J. Marin received her Ph.D. in chemistry from Arizona State University. She has expertise in sample preparation, liquid chromatography, and mass spectrometry, and has gained over 10 years of experience developing and validating clinical assays from her tenure at the ARUP Institute for Clinical and Experimental Pathology.  She has additional experience doing analytical work on polymers, adhesives, coatings, food packaging, and other specialty chemicals. Stephanie has worked in applications development and marketing for an HPLC instrument and column manufacturer, and as a supervisor at an EPA certified lab. She is the author of over 30 peer reviewed publications and book chapters and over 80 abstracts presented at national meetings.

Authorship: (1) Stephanie J. Marin, Ph.D., (2) Simuli L. Wabuyele, Ph.D., (3) Gwen A. McMillin, Ph.D.
(1) Biotage, Charlotte, NC, (2) ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, UT, (3) ARUP Laboratories, University of Utah Health Sciences Center, Salt Lake City, UT

Short Abstract The development and validation of an LDT for drug detection implementing a new specimen type for routine clinical use creates multiple challenges. A clinical assay to detect neonatal drug exposure using umbilical cord tissue was developed and validated. Part 1 of the case history will review assay conception, clinical utility, proof-of-concept studies, method development and validation for this complex biological matrix. Homogenization techniques, drug extraction, sample clean-up, and LC-MS detection platforms that were evaluated will be discussed. Results used to determine final method parameters and conditions, and criteria for routine clinical use will be presented.

Long Abstract

There is a misconception that once a developed and validated method goes live in the clinical lab, that is the end of the story; however, often issues with the performance of a clinical assay are discovered after months or years in the production lab. Assays often undergo modifications during their lifetime to address key issues with analytical/clinical performance, workflow, turn-around time, cost or increasing sample volumes. Many laboratory developed tests are eventually completely reworked and revalidated to meet the demands/needs for routine clinical utilization. This presentation will focus on the history of a clinical assay to detect drugs and drug metabolites in umbilical cord tissue by LC-MS/MS as an example.

Part 1 will review proof of concept studies, method development and initial validation of the assay. Part 2 discusses subsequent changes that were validated and implemented over time in the production lab and their effect on the performance of the assay. Part 3 presents how the assay was reworked and its status today.

References & Acknowledgements:

1. Marin SJ, Christensen RD, Baer VL, Clark CJ, McMillin GA., Ther Drug Monit. 2011 Feb;33(1):80-5.

2. Marin SJ, Metcalf A, Krasowski MD, Linert BS, Clark CJ, Strathmann FG, McMillin GA., Ther Drug Monit. 2014 Feb;36(1):119-24.

3. Haglock-Adler CJ, McMillin GA, Strathmann FG., Clin Biochem. 2016 Sep;49(13-14):1092-5.

Financial Disclosure

IP Royalty: no

Planning to mention or discuss specific products or technology of the company(ies) listed above:

yes