In this interview, News Medical speaks with Dennis Dietzen, PhD, clinical chemist and laboratory medicine expert, about the evolution of toxicology screening, the limitations of traditional immunoassays, and the development of direct-to-definitive toxicology screening using mass spectrometry. He discusses how false positives and false negatives can impact patient care, particularly in pediatric settings, and explains how advanced analytical technologies are transforming clinical toxicology testing.
Can you please explain your role?
I am a clinical chemist with a longstanding interest in toxicology testing and laboratory medicine. Much of the work I will discuss today was developed during my time at Washington University in St. Louis Children’s Hospital, where I spent more than two decades working to improve toxicology testing and patient care.
More recently, I have been focused on implementing similar approaches within a pediatric healthcare system in Phoenix and exploring how these innovations can be adapted to different clinical environments.
What inspired your interest in improving toxicology screening methodologies?
My interest dates back to my fellowship years when homogeneous immunoassays were becoming increasingly popular. While these assays offered speed, convenience, and relatively low cost, it quickly became apparent that they also had significant limitations.
Even then, I believed there had to be a better way to perform toxicology testing. It ultimately took nearly three decades to reach the point where we could realistically replace many traditional screening methods with direct mass spectrometry-based approaches, but that goal remained constant throughout my career.
Why have immunoassays remained the dominant approach for toxicology screening for so long?
Immunoassays were transformative because they replaced much more labor-intensive techniques, such as paper chromatography, thin-layer chromatography, and gas chromatography-mass spectrometry workflows that often required extensive sample preparation and highly specialized expertise. They were fast, automated, reproducible, and relatively inexpensive.
Another important factor is that many of these assays were originally developed for workplace toxicology testing rather than clinical toxicology,so their primary purpose was to identify toxicology concentrations associated with workplace impairment while minimizing false positive results that could have legal consequences.
Over time, these assays became deeply embedded in clinical practice despite not being specifically designed for many of the patient populations we serve today.
What are the fundamental limitations of immunoassays when detecting toxicology?
The core issue is that antibodies evolved to recognize relatively large biological structures such as proteins and peptides. Toxicology molecules, by contrast, are very small. Since antibody binding sites are much larger than the toxins they are intended to detect, structurally similar compounds can also bind and generate a signal.
This creates an inherent challenge. Molecules that share certain chemical features with the target toxicology may trigger a positive result even when the toxin of interest is not present. That limitation is built into the biology of antibody-based detection and is one reason why immunoassays can never achieve the same specificity as mass spectrometry.
False positives are widely discussed, but you also emphasize false negatives. Why is that important?
Most laboratorians and clinicians are familiar with the false positive problem. However, false negatives may be an even greater concern in some clinical settings. Many toxicology screening immunoassays were designed with relatively high cutoff concentrations because they were intended for workplace testing. As a result, clinically meaningful toxin exposures can sometimes go undetected.
When clinicians receive a negative result, they often assume that no relevant toxin is present. In reality, the patient may have been exposed to a substance that falls below the assay threshold or is not adequately recognized by the antibody. This can have serious consequences when clinical decisions are based on those results.
How can inaccurate toxicology screening results affect patient care, particularly in pediatrics?
The stakes can be extraordinarily high. In pediatric medicine, toxicology results may influence decisions about child safety, discharge planning, and involvement of child protection services, as physicians often need to decide whether a child can safely return to a home environment or requires protective intervention.
An inaccurate result in either direction can have profound consequences. A false positive may expose families to unnecessary investigations and separation, while a false negative may fail to identify an unsafe environment. Improving analytical accuracy is therefore a patient safety issue, as much as a laboratory issue.
Can you share examples of the real-world consequences of false positive toxicology screens?
There have been several highly publicized cases. One involved a pregnant woman who tested positive for opiates after consuming food containing poppy seeds. As a result, she became the subject of scrutiny by child welfare authorities and temporarily lost access to her children while the result was challenged.
There have also been cases within correctional systems where changes in testing reagents dramatically increased positive screening rates without any actual increase in toxin use. These situations highlight how analytical limitations can create significant personal, legal, and societal consequences.
What is direct-to-definitive toxicology screening, and how does it differ from traditional testing workflows?
Direct-to-definitive toxicology screening replaces the traditional two-step process of immunoassay screening followed by confirmatory testing. Instead of relying on a preliminary antibody-based screen, samples are analyzed directly using highly specific mass spectrometry methods.
This approach provides definitive identification from the outset, reducing uncertainty and eliminating many of the limitations associated with immunoassays. Rather than asking whether a specimen reacts like a particular toxin class, mass spectrometry directly identifies the compounds that are present, providing a much more accurate representation of patient exposure.
What challenges have you encountered while implementing this approach in different healthcare systems?
One of the most interesting lessons has been realizing that success depends on more than just technology; what worked exceptionally well in St. Louis cannot necessarily be copied and pasted into a different healthcare environment.
Patient populations, testing demands, clinical workflows, and institutional priorities vary considerably. As I have worked to replicate this model in Phoenix, I have come to appreciate the importance of adapting implementation strategies to local circumstances while maintaining the same commitment to analytical excellence and patient care.
Looking ahead, what do you believe is the future of toxicology screening?
I believe the future lies in moving away from screening technologies that were designed for a different era and toward direct analytical methods that provide definitive answers. Mass spectrometry continues to become faster, more accessible, and more practical for routine clinical use.
As laboratories increasingly recognize the false positive and false negative limitations of immunoassays, I expect more institutions to adopt direct-to-definitive testing strategies. Ultimately, our responsibility is to provide clinicians with the most accurate information possible, and modern mass spectrometry offers a pathway toward achieving that goal.
About Dennis Dietzen, PhD
Dennis J. Dietzen, PhD, is a distinguished clinical chemist and laboratory medicine leader with extensive expertise in clinical toxicology, pediatric laboratory medicine, and diagnostic innovation. He spent more than two decades at Washington University School of Medicine in St. Louis and St. Louis Children’s Hospital, where he held leadership roles in clinical chemistry and laboratory operations.
Throughout his career, Dr. Dietzen has focused on improving diagnostic accuracy and translating advanced analytical technologies into routine clinical practice. His research interests include mass spectrometry, pediatric laboratory medicine, clinical toxicology, biomarker development, and laboratory quality improvement.
Dr. Dietzen has authored numerous peer-reviewed publications and has contributed significantly to national laboratory medicine initiatives through leadership positions in professional organizations, including the Association for Diagnostics & Laboratory Medicine (ADLM).
Known for advocating evidence-based laboratory practices, Dr. Dietzen has been a strong proponent of replacing traditional screening approaches with more accurate definitive testing methods. His work has helped advance the use of mass spectrometry in clinical laboratories, improving the reliability of toxicology testing and supporting better patient care outcomes, particularly in vulnerable pediatric populations.
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