Forensic Toxicology: Meeting the Demands of Two Slaves—Science and the Law

The poisoning of living things takes two forms, accidental and purposeful, with both resulting in potentially disastrous outcomes. Whether poisoning results in aberrant behaviors, hospitalizations, or deaths, the field of forensic toxicology plays a key factor in relating analytical findings to correlation of effects. As a “forensic” science, forensic toxicology uses the principles of analytical chemistry to identify potentially causative agents and toxicology to offer mechanistic reasons for impairment, illness, or death with the distinct applicability of these sciences to matters of the law. In these respects, the practicing forensic toxicologist must understand the need for solid science that is research and empirically based as the core in order to meet the ever-increasing demands placed on the practitioner in the medico-legal setting.

The four areas of influence of forensic toxicology include:

  1. Human Performance Toxicology—the identification and interpretation of substances that impair an individual’s ability to perform a task, e.g., driving an automobile or athletics
  2. Postmortem Toxicology—the identification of substances in the body that aid in the determination of cause and manner of death
  3. Workplace Testing—the screening of body fluids or tissues from individuals relating to employment or impairment while employed, e.g., applying for a job
  4. Drug Courts/Probation and Parole—court-ordered testing related to individuals who, as part of some program, must remain drug free. 

Regardless of the application, the forensic toxicologist must employ processes that can withstand harsh scrutiny both from other scientists and legal proceedings.

The science

The analytical phase of forensic toxicology has undergone vast change since its inception in the mid-19th century.1 No longer are nonspecific tests, e.g., color reactions, acceptable for purposes of scientific proof of the presence of some substance of concern. As analytical tools have progressed, so have the expectations of the field. Today, the hallmark of a good forensic toxicological identification is predicated on the use of two different analytical techniques employing two different physicochemical principles wherever possible, with at least one of the techniques employing some sort of molecular identification.2

The most common molecular-based tools in play at present in the majority of forensic toxicology laboratories are hyphenated mass spectrometric techniques. While gas chromatography-mass spectrometry (GC-MS) was the mainstay through most of the 1980s for analysis of organic substances, including drugs, a transition to liquid chromatography-mass spectrometric (LC-MS) techniques has occurred. For metals, inductively coupled plasma-mass spectrometry (ICP-MS) and optical emission spectroscopy (OES) are fairly common tools, and other techniques, e.g., ion chromatography, are also used for sundry other substances of toxicological concern. In respect to LC-MS, single-stage technologies have given way to multistage (LC-MS/MS) or time-of-flight (LC-TOF) processes, both requiring relatively simpler sample preparation while giving improved sensitivity and specificity compared to older analytical tools.

The metamorphosis of LC-MS in the last 20 years has been remarkable. A good example of the changes in this technique can be found in the Waters Corp. (Milford, MA) genesis of benchtop LC-MS instruments. In only approximately 20 years, this group went through a series of changes from its Platform single-stage LC-MS, to its Micro LC-MS-MS, to improved tandem devices (Premier, TQD, TQS) and TOF instruments, each providing improvements in specificity, sensitivity, ruggedness, ease of use, software, and issue-based solutions.

With the advent of new drugs (both licit and illicit) and other chemical exposures as well as new regulatory expectations, the challenges facing the forensic toxicologist today are as formidable as ever before. Method validation requirements, stringent identification criteria, and the ability of instruments today to detect very low concentrations of substances (the “vanishing zero”) further contribute to the analytical challenges in forensic toxicology.

Interpreting analytical findings in respect to correlation to effects ranging from impairment to death can be extremely challenging. Variables such as differences in metabolism, anatomical source of a given specimen, postmortem movement of chemicals in the body, etc., all create uncertainties in any interpretation in the absence of additional information, e.g., circumstances, observations, and so on. As such, analytical schemes and interpretive accuracy must be based on a holistic approach to any given case that takes into account such things as case history, specimen collection information, medical history, and timing of events.

The law

Science tends to be truth seeking, while one function of the law is to settle disputes. This dichotomy does not always make for good bedfellows. It is incumbent, however, upon the forensic scientist to understand that he or she is not an advocate, whereas that is the role of an attorney, i.e., to advocate for his or her client.

In the adversarial judicial system within the United States, challenges to the science used in criminal and civil cases can be contentious, often with mistrust on both sides. That attorneys are skeptical of forensic science is somewhat grounded in truth with manifold examples of forensic science investigations gone awry.3–5 For their part, however, the majority of forensic scientists are hard-working, dedicated, significantly educated, and trained individuals who perform their jobs with the utmost of care and caution

In 2009, the National Academy of Sciences issued a report entitled, Strengthening Forensic Science in the United States: A Path Forward.6 This report was commissioned by the U.S. Congress. While there were many findings delineated in the report, the critical focus was on forensic disciplines where pattern-matching is the basic tenet of identification, e.g., fingerprinting, bite marks, bullet comparisons, etc. The major criticisms were based on a lack of scientific principles supporting claims. A few forensic sciences were lauded for strong scientific merit, including forensic toxicology. Nevertheless, it was recognized that all branches of forensic science must be steeped in science, have a strong scientific research component, and be statistically sound. Currently, initiatives from both the executive and legislative branches of the U.S. Federal Government are being considered to assist the forensic sciences to reach these goals.

In 1997, with updates in 1997, 2002, and 2006, the Toxicology section of the American Academy of Forensic Sciences (AAFS) and the Society of Forensic Toxicologists established guidelines for the practice of forensic toxicology.7 Prior to this time, forensic toxicology laboratories were more or less left to their own devices in respect to quality initiatives. This former attempt at self-regulation was ahead of its time and firmly established this discipline as one of the leaders in promoting quality standards. Unfortunately, specified as “guidelines,” laboratories were not obligated to follow these recommendations, thus rendering no universal acceptance for this document.

In October 2009, the Scientific Working Group in Toxicology (SWGTOX) was established.8 Scientific working groups in the forensic sciences are long-standing, with each discipline having its own working group, e.g., SWGDAM for DNA analysis. The function of these groups is to define the standards of practice and best practices within each discipline. These groups were initially supported financially and structurally by the U.S. Department of Justice and now by the National Institute of Standards and Technology (NIST). It is the intention of NIST to refer to these groups as Guidance Groups with details of structure and function still to be determined. Regardless of their title, in part, these groups are designed to strengthen the forensic sciences due to the concerns raised by the NAS report and other observations.

SWGTOX is comprised of forensic toxicology practitioners, academics, and other subject matter experts deemed necessary, representing governmental, private, and not-for-profit concerns. Standards development involves a process that allows all stakeholders affected by such standards to review and comment before adoption of the standard. To date, standards regarding such issues as a code of professional conduct, method validation, research, development, testing, and evaluation have been adopted. Near term, additional standards on quality control, mass spectrometry, personnel requirements, and accreditation will be adopted. Other aspects of forensic toxicology, e.g., identification standards, will be forthcoming. While there is no enforcement mechanism currently assigned to the SWGs, it is anticipated that the failure of laboratories to adopt such standards will be problematic as these facilities are confronted with them in the courtroom.

Forensic toxicology practitioners and laboratories can be certified and accredited, respectively. As in the field of medicine, where board certification does not guarantee excellence in the clinician, certification and accreditation do not guarantee superior practices by a forensic toxicologist or laboratory; however, they do demonstrate minimally acceptable knowledge and practices. In sum total, though, adherence to SWGTOX standards and certification/accreditation should provide confidence to the general public and the legal system that any given individual or laboratory is meeting the needs of a quality-based forensic toxicology system.


Forensic toxicology plays a significant role in both public health and public safety. At the foundation of this discipline are two established sciences, analytical chemistry and toxicology. When practiced correctly, forensic toxicology aids medical examiners, law enforcement, attorneys, clinicians, and others by establishing the identification of potential poisoning or impairing agents and related interpretive value to these findings. Adherence to sound quality practices not only meets the needs of the discipline, but allows use of the findings in matters of the law. Through adoption of existing and future quality standards, questions regarding the validity of forensic toxicology as an applied science are addressed in a scientifically sound manner. After all, whether it is for purposes of the law or pure research, nothing beats the scientific process.


  1. Middleberg, R. Forens. Mag. 2008, 5, 16–23.
  2. Jones, G. In: Clarke’s Analysis of Drugs and Poisons; Pharmaceutical Press: London, U.K., 2011; Vol. 1; pp 176–89; ISBN 978-0-85369-711-4.
  3. Thompson, W. Southwestern Law Rev.  2008, 37, 1027–50.
  4. drug-lab-scandal-should-get-years-guilty-plea-attorney-general- says/7CAxybo8rldtZIKSMgSH3L/story.html (accessed 8 Nov 2013).
  5. (accessed 8 Nov 2013).
  6. Edwards, H.T.; Gatsonis, C. Strengthening Forensic Science in the United States: A Path Forward; National Academies Press: Washington, DC, 2009; ISBN 978-0-309-1315-3.
  7. SOFT/AAFS Guidelines Committee, SOFT/AAFS Forensic Toxicology Laboratory Guidelines, Mesa, AZ. Society of Forensic Toxicologists and American Academy of Forensic Sciences (Toxicology Section), 2006.
  8. (accessed 8 Nov 2013).

Robert A. Middleberg, Ph.D., is Laboratory Director and Vice President, Quality Assurance, NMS Labs, 3701 Welsh Rd., Willow Grove, PA 19090, U.S.A.; tel.: 215-366-1226; fax: 215-366-1668; e-mail: