In October 2025, Laboratory Director and Chief toxicologist Laureen Marinetti, PhD, made presentations at both the National Association of Medical Examiners 2025 Conference in Louisville, Kentucky, and at the Society of Forensic Toxicologists 2025 Conference in Portland, Oregon.

NAME 2025 Recap #1: Propoxyphene 

At this year’s NAME meeting, Laureen Marinetti presented Propoxyphene was taken off the Market Fifteen Years Ago, and Yet the Lab is still Confirming it in Toxicology Casework. This presentation was developed in conjuction with her fellow Axis toxicologists, Kevin Shanks and Stuart Kurtz.

Dextro-propoxyphene was introduced for clinical use in 1963 as an opioid pain reliever for mild to moderate pain.  It was sold under various names as a single-ingredient product (e.g., Darvon or Wygesic), or as part of a combination product which could contain acetaminophen, aspirin, phenacetin, and/or caffeine (e.g., Darvocet, Darvon Compound-65).  The most frequent side effects of propoxyphene include lightheadedness, dizziness, sedation, nausea, and vomiting.  However as the drug continued to be used it was discovered that, even during proper therapeutic use, it was cardio-toxic.  Taken at therapeutic doses, there were significant changes to the electrical activity of the heart: prolonged PR interval, widened QRS complex and prolonged QT interval.  In November of 2010 the FDA released a drug safety communication that recommended against the continued use of dextro-propoxyphene.  Levo-propoxyphene (FDA approved in 1962) was available as an antitussive (Novrad) with no opioid like effects, however it was removed from the market in the 1970s.  Eight cases confirmed positive for propoxyphene and/or norpropoxyphene in cases received by the lab from January 2020 to April of 2025.  The eight cases were from the following States; Arizona (2), Florida (2), Kentucky (1), Michigan (1), and Ohio (2).  Since this presentation there has been at least one additional case confirmed.  Of these 8 cases there was only one in which propoxyphene may have played a role in the cause of death.  This data shows that old drugs should never be counted out.  Somehow they have a way of making an appearance just when you thought you would probably never see them again.   

References

• Wilsa J. Raymonvil, George Hime, and Diane Moore, “Propoxyphene – Gone but not Forgotten”, Poster 27 presented at the Society of Forensic Sciences annual meeting in St. Louis, MO., 2024.  
• Baselt, Randall C., Disposition of Toxic Drugs and Chemicals in Man, 12th Edition, Biomedical Publications, 2020.

NAME 2025 Recap #2: Drug Screening of Vitreous Fluid 

Laureen Marinetti presented Case Comparisons of Blood, Vitreous Fluid, and Urine (Where Available): Update:  Drug Screen Findings in Over 200 Cases. This presentation was also developed in conjuction with her fellow Axis toxicologists, Kevin Shanks and Stuart Kurtz.

Vitreous fluid is located in the eye between the retina and the lens.  It is made up of ~ 99% water but 2 to 4 times more viscous. Vitreous fluid is commonly tested for electrolytes, glucose, creatinine, urea nitrogen, heroin exposure, recent cocaine use, and to help determine the absorption state of ethanol.  It can also be tested as a second specimen to confirm drug findings from another matrix. Depending upon the circumstances of a death, vitreous fluid may be the best or only specimen available for toxicology testing. Data regarding the presence and concentration of drugs in vitreous fluid as compared to whole blood is limited.  Drug penetration in to vitreous fluid depends on various factors:  blood concentration, physicochemical and pharmacological properties, distribution volume, protein binding and blood retinal barrier (BRB) permeability.  Drugs may diffuse passively or be actively transported across the BRB.  Confirmed drug findings in over 1000 cases (more cases were added after the abstract was turned in to NAME) were compared between blood, vitreous fluid, and urine, where available. These data are important to help determine if a specific drug would be expected to be detected in vitreous fluid. Knowledge of the limitations of using vitreous fluid as a matrix in which to perform general drug screening is necessary for the proper interpretation of the results.  Commonly encountered drugs did confirm in vitreous fluid with the exception of cannabinoids. In fact, a lingering opioid death may be able to be determined by comparing blood and vitreous fluid concentrations. Cases involving fentanyl will were presented as examples. Vitreous fluid can be useful in the detection of some drugs but not all drugs. In an acute overdose, drugs may not have had enough time to pass into the vitreous fluid before death occurred, an example of such a case will be presented. Also drugs at lower concentrations in blood may not be detectable in vitreous fluid, as well as those drugs that are lipophilic like benzodiazepines. Vitreous fluid has its place in toxicology testing, however due to its’ limitations, using it as a specimen for general drug screening should be avoided.  

References 

• Erin B. Divito, Jedediah I. Bondy, Zachary J. DiPerna, Frederick W. Fochtman, and Christopher B. Divito.  A comparison of vitreous fluid and blood matrices in postmortem drug analysis, Jrn. of Analytical Toxicol., 2025, Vol 49, 351-357. 
• Fabien Be´valot, Nathalie Cartiser, Charline Bottinelli, Laurent Fanton, and Je´roˆme Guitton, Vitreous humor analysis for the detection of xenobiotics in forensic toxicology: a review, Forensic Toxicol., 2015. 
• Anna Pelander, Johanna Ristimaa, and Ilkka Ojanperä, Vitreous Humor as an Alternative Matrix for Comprehensive Drug Screening in PostmortemToxicology by Liquid Chromatography–Time-of-Flight Mass Spectrometry, Jrn. of Analytical Toxicol., 2010, Vol 34, 312-318. 

SOFT 2025 Recap: GHB

Laureen Marinetti presented Gamma Hydroxybutyrate:  What Does the Concentration Mean?  Review of Ante-mortem and Postmortem Casework from 2020 – 2025.  Laureen J. Marinetti, Ph.D, F-ABFT, Kevin G. Shanks, M.S., D-ABFT-FT, and Stuart A. K. Kurtz, M.S., D-ABFT-FT.  The abstract (S-58) is available upon request.

Gamma hydroxybutyrate (GHB) is an endogenous molecule, a prescription drug, an illicit drug, and can be formed both ante-mortem and postmortem, making interpretation difficult.  As an endogenous molecule, GHB acts as a neuromodulator with primary activity at the gamma- aminobutyrate B (GABAB) receptor; it is also a minor metabolite of GABA.  Clinically, GHB was first used in the 1960s as an adjunct to anesthesia but was unpredictable regarding its duration of effect, likely due to its steep dose response curve.  GHB is now used clinically to treat narcolepsy and alcohol withdrawal syndrome.  As an illicit drug, GHB can be derived from its precursors, gamma butyrolactone (GBL), and 1,4-butanediol (1,4-BD), both are industrial solvents.  GHB can be elevated in blood samples collected in sodium citrate tubes, and GHB can increase postmortem during the decomposition process.  

The data reviewed consisted of a total of 402 ante-mortem and postmortem cases sent to the lab that were tested for GHB, either as directed testing or as part of a drug panel.  GHB testing in postmortem cases resulted in 20 positive bloods, and 1 positive urine sample, out of 31 cases that were directed for GHB testing.  There was a total of 9 ante-mortem blood and urine samples positive for GHB out of a total of 371 cases (2.4%) tested in the drug facilitated assault panel.  Selections of these cases were presented. 

The Axis cases in which GHB use was suspected were not always the cases with the highest GHB concentration.  Review of the literature shows various cut offs proposed for postmortem blood and urine GHB to try to differentiate between endogenous and exogenous GHB.  The cut offs vary from 20 to 50 mcg/mL in blood, and 10 to 30 mcg/mL in urine.  In the Axis postmortem cases there were 7 blood samples with a GHB of less than 20 mcg/mL, 2 cases less than 30 mcg/mL, and no cases greater than 30 and less than 50 mcg/mL.  The concentration range of GHB for all postmortem samples was 6.0 to 1668 mcg/mL.  The endogenous GHB cut offs for ante-mortem blood and urine commonly used are 2, and 10 mcg/mL, respectively.  In the five Axis ante-mortem blood cases there was a GHB concentration median of 74 and a mean of 59.7 mcg/mL, with a range of 6 to 78.2 mcg/mL.  In the four Axis ante-mortem urine positive GHB cases, there were two cases less than 10 mcg/mL, a median of 8.7 and a mean of 11.7 mcg/mL, with a range of 7.5 to 248 mcg/mL.    

In a 2025 study of 525 cases where no exogenous GHB use was suspected, 85% of the cases showed evidence of GHB formation postmortem, with a urine/blood ratio median of 0.52. Postmortem GHB in blood was usually less than 50 mcg/mL, but not always, 30% were above 50 mcg/mL.  It was proposed that a urine/blood ratio of greater than 2.0 suggested exogenous use of GHB, however 15% of these cases had blood GHB of less than 50 mcg/mL.  It was also suggested that a longer post mortem interval (PMI) resulted in a greater chance of GHB formation postmortem (Arnes et. al. 2025).   

Interpretation of GHB in postmortem blood can be problematic.  A detailed history and the ability to test additional specimens such as urine and vitreous fluid may be necessary. 

References 

• Marit Arnes, Hilde Marie Eroy Edvardsen, Line Berge Holmen, Lena KIristoffersen, and Gudrun Hoiseth, Post-mortem formation of GHB:  A retrospective study of forensic autopsies, Forensic Science International 2025, 372.
• Jennifer L. Smith, Shaun Greene, David McCutcheon, Courtney Weber, Ellie Kotkis, Jessamine Soderstrom, et.al., A multicentre case series of analytically confirmed gamma-hydroxybutyrate intoxications in Western Australian emergency departments: Pre-hospital circumstances, co-detections and clinical outcomes, Drug and Alcohol Review, 2024; 1-13.
• A.W. Jones, A. Holmgren F.C., Kugelberg, and F.P. Busardò, Relationship Between Postmortem Urine and Blood Concentrations of GHB Furnishes Useful Information to Help Interpret Drug 
• Intoxication Deaths, Journal of Analytical Toxicol, 2018, Vol 42, 587-591.