A medical examiner signs out another fentanyl death. The scene, the prescription history, and the confirmed toxicology all point the same direction, so the case closes as a straightforward opioid overdose. The gabapentin the decedent had taken for months never reaches the report, because it was never on the confirmation panel to begin with.
Gabapentin appears in roughly 1 in 10 US overdose deaths where postmortem toxicology was performed, and in about 85 to 90 percent of those cases an opioid is co-detected. That is the headline finding from the CDC’s analysis of State Unintentional Drug Overdose Reporting System (SUDORS) data covering 23 states and the District of Columbia for 2019 and 2020, which identified gabapentin in 9.7% (5,687 of 58,362) of overdose deaths with documented toxicology results [1]. A 2024 PAIN cohort study drawing on UK primary care data reinforced the pattern from the prescribing side, with elevated overdose and misuse risk concentrated among patients also taking opioids, benzodiazepines, antidepressants, or Z-drug hypnotics [2].
The operational finding behind these numbers is more pointed: many postmortem laboratories are not detecting gabapentinoids at all, because gabapentin and pregabalin are not on the default LC-MS/MS confirmation panel that most laboratories built years ago. Even when fentanyl explains the death, a gabapentinoid that contributed to prolonged sedation, respiratory depression, or naloxone-resistant outcomes can remain invisible in the toxicology report, with downstream effects on contributory cause language, manner determination, and case interpretation.
UTAK has spent five decades building QC materials for the laboratories that run up against these exact analytical blind spots. Gabapentinoids represent a familiar pattern: a class of compounds that quietly accumulated forensic relevance while sitting outside the default range that many older panels are designed to detect. The under-detection is not a question of analytical capability; nearly every laboratory running LC-MS/MS could add gabapentin and pregabalin tomorrow. The question is whether the case mix justifies the addition, and increasingly, the answer is yes.
Why gabapentinoids fell off default panels
It is worth acknowledging how we got here, because the panel decisions made in earlier years were entirely defensible at the time. Gabapentin was approved by the FDA in the early 1990s as a non-controlled substance with no recognized abuse potential, and for most of the next two decades the medication was prescribed widely for off-label indications and rarely flagged in suspected overdose deaths [3]. Pregabalin followed a similar trajectory after its 2004 approval, although it was assigned federal Schedule V status because of pre-marketing dependence signals. With no demonstrated forensic relevance and prescription history readily available through medical record review, gabapentin was a reasonable analyte to defer when laboratories built their LC-MS/MS panels.
That picture has shifted. Buyers and abusers have learned that gabapentinoids potentiate opioid effects, the overdose surveillance data has caught up with that reality, and the CDC has explicitly noted the value of including gabapentin in postmortem testing in jurisdictions where it is feasible [1]. The analytical reasoning that supported exclusion in 2010 does not necessarily support exclusion in 2026.
What the Polysubstance Data Shows
The CDC MMWR report identified 5,687 overdose deaths with gabapentin detected in postmortem toxicology, and of those, approximately 52 percent had gabapentin determined to have contributed to the cause of death [1]. The opioid co-involvement was not incidental; it was the dominant pattern, with illicitly manufactured fentanyl driving most of the increase across the study period. Gabapentinoid involvement in fatal cases tracks closely with co-prescribed CNS depressants and illicit opioid use, which means it is not evenly distributed across casework: it concentrates in exactly the cases where polysubstance interpretation matters most.
For postmortem laboratories, the practical implication is that cases presenting as straightforward fentanyl deaths may have a gabapentinoid component that affects manner determination, contributory cause language, and case interpretation. Without targeted testing, that component remains invisible.
State-level Scheduling Has Reshaped the Regulatory Picture
Several states have responded to gabapentin’s evolving risk profile by reclassifying it as a Schedule V controlled substance, beginning with Kentucky in July 2017, followed by Tennessee and West Virginia in 2018, North Dakota, Virginia, and Alabama in 2019, Utah in 2024, and most recently Montana in 2025 [4]. Michigan also scheduled gabapentin during this period but later rescinded the policy. Pregabalin has been a federal Schedule V drug since 2005, scheduled by the DEA shortly after its 2004 FDA approval, and an additional 17 jurisdictions require gabapentin reporting through their PDMPs without formal scheduling [4].
For toxicology laboratories, scheduling actions in your jurisdiction can change the chain-of-custody, reporting, and PDMP data available for case interpretation. They also signal that prosecutors, medical examiners, and public health partners are beginning to treat gabapentinoid involvement as forensically meaningful. Laboratories without these analytes on panel can find themselves answering questions they cannot answer from existing data.
Analytical Considerations for Adding Gabapentinoids
Adding gabapentin and pregabalin to an LC-MS/MS confirmation panel is generally a targeted addition rather than a major method redesign. Both compounds are amenable to standard reversed-phase chromatography with positive-mode electrospray ionization, and validated methods are well established. A few interpretive considerations matter more than the chemistry.
Therapeutic ranges anchor case interpretation
Reported therapeutic plasma ranges for gabapentin generally fall around 2 to 20 mg/L, and for pregabalin approximately 1 to 10 mg/L, although these vary by source and indication [5]. In postmortem casework, concentrations need to be evaluated against these ranges rather than against arbitrary cutoffs.
Renal clearance complicates interpretation
Both gabapentinoids are predominantly renally cleared, and neither is significantly metabolized. Patients with reduced renal function can present with elevated steady-state concentrations even at therapeutic doses, so reviewing antemortem renal function (where available) is essential before characterizing a concentration as supratherapeutic.
Femoral blood and polysubstance context drive interpretation
Studies of postmortem gabapentin distribution suggest limited postmortem redistribution, with femoral blood providing the most interpretable specimen [6]. For pregabalin, recent forensic literature has proposed femoral concentrations of approximately 20 mg/L or higher as a “cause for concern” threshold, with lower concentrations interpreted in the context of tolerance and co-detected substances [7]. Even subtherapeutic or therapeutic gabapentinoid concentrations can be forensically meaningful when an opioid, benzodiazepine, or alcohol is co-detected, and reporting language should reflect this combined risk rather than treating the gabapentinoid as an incidental finding.
The Case for Panel Inclusion
The argument for adding gabapentinoids is not that every case requires confirmation. It is that the cases where these compounds matter (polysubstance opioid deaths, sedation deaths with ambiguous toxicology, cases with prior gabapentinoid prescriptions) cannot be identified in advance from scene context alone. Without targeted testing, the panel is being asked to answer questions it was not built to answer.
For laboratories considering this addition, matched-matrix QC materials are essential to validate method performance across the concentration ranges seen in casework. UTAK’s Purpose-Built controls allow laboratories to specify gabapentinoid analytes and concentrations for method development, while our stock urine quality controls cover routine performance monitoring across drugs of abuse panels. Our Understanding Toxicology post offers broader clinical and analytical framing, and our Common QC Failures guide outlines the systematic review process we use when troubleshooting unexpected results during method expansion.
Key Takeaways: Gabapentinoid Panel Readiness Checklist
☐ Polysubstance review completed: case mix evaluated for gabapentinoid-relevant scenarios (opioid co-detection, prior gabapentinoid prescriptions, ambiguous sedation)
☐ Method capability confirmed: LC-MS/MS panel can accommodate gabapentin and pregabalin without major redesign
☐ Therapeutic ranges documented: laboratory has reference ranges and renal-clearance considerations available for interpretation
☐ Matrix-matched QC sourced: control materials cover therapeutic and elevated concentration ranges seen in casework
☐ Reporting language reviewed: contributory-cause and polysubstance language updated to reflect gabapentinoid findings
☐ Jurisdictional scheduling tracked: state-level Schedule V status monitored for chain-of-custody and PDMP implications
Frequently Asked Questions
Does gabapentin show up on a standard drug test?
Generally, no. Most routine immunoassay drug screens, including standard 5- and 10-panel urine immunoassays, do not include gabapentin or pregabalin. Detection requires a targeted method, typically LC-MS/MS, with the analyte specifically included in the panel.
What is the therapeutic range for gabapentin and pregabalin?
Reported plasma therapeutic ranges generally fall around 2 to 20 mg/L for gabapentin and 1 to 10 mg/L for pregabalin, although ranges vary by source and indication. Renal function significantly affects steady-state concentrations and should be considered in case interpretation.
Why is pregabalin abused, and how does it differ from gabapentin?
Both gabapentinoids can produce euphoria, sedation, and CNS depression at supratherapeutic doses, and both potentiate opioid effects. Pregabalin generally has higher bioavailability and a faster onset, which has made it more commonly diverted in some regions. Pregabalin is federally Schedule V; gabapentin is scheduled only at the state level.
Should our laboratory add gabapentinoids to its routine panel?
For laboratories with substantial postmortem opioid casework, the case for inclusion is strong given the documented co-involvement rate. The decision should be based on the case mix you actually see and on your medical examiner’s or coroner’s interpretive needs.
How are postmortem gabapentinoid concentrations interpreted?
Femoral blood is the preferred specimen because of limited postmortem redistribution. Concentrations are interpreted against therapeutic ranges, renal function, and co-detected substances, rather than against fixed cutoffs. Recent forensic literature has proposed pregabalin concentrations of approximately 20 mg/L or higher in femoral blood as a ’cause for concern’ threshold.
Looking ahead
Our technical team has worked with forensic and clinical laboratories adding novel analytes to existing methods for decades. Gabapentinoids fall into a category of additions that are technically straightforward but interpretively nuanced. If you are evaluating whether your panel captures the polysubstance picture in your casework, or working through QC requirements for a method expansion, we are here to talk it through. Reach out at welovecontrol@utak.com or call 888.882.5522.
References
[1] Mattson CL, Chowdhury F, Gilson TP. Notes from the Field: Trends in Gabapentin Detection and Involvement in Drug Overdose Deaths, 23 States and the District of Columbia, 2019-2020. MMWR Morb Mortal Wkly Rep. 2022;71(19):664-666.
[2] Muller S, Bailey J, Bajpai R, Helliwell T, Harrisson SA, Whittle R, Mallen CD, Ashworth J. Risk of adverse outcomes during gabapentinoid therapy and factors associated with increased risk in UK primary care using the clinical practice research datalink: a cohort study. PAIN. 2024;165(10):2282-2290.
[3] U.S. Drug Enforcement Administration, Diversion Control Division. Gabapentin (Trade Name: Neurontin) Drug Fact Sheet.
[4] Gora Combs K, Vickers-Smith R, Stewart C, Wacker D, Hincapie-Castillo JM. A comprehensive analysis of jurisdiction-specific laws related to scheduling or required prescription drug monitoring of gabapentin in the United States, 2016-2024. Int J Drug Policy. 2025;147:105064.
[5] Schulz M, Iwersen-Bergmann S, Andresen H, Schmoldt A. Therapeutic and toxic blood concentrations of nearly 1,000 drugs and other xenobiotics. Crit Care. 2012;16(4):R136.
[6] Hamm CE, Gary RD, McIntyre IM. Gabapentin concentrations and postmortem distribution. Forensic Sci Int. 2016;262:201-203.
[7] Nahar LK, Paterson S. Pregabalin concentrations: establishing ‘normal’ and ’cause for concern’ concentration ranges in postmortem blood. J Anal Toxicol. 2025;49(4):272-279.
