Analysis of suzetrigine, a novel non-opioid pain medication, in whole blood and urine using liquid chromatography-tandem mass spectrometry

Suzetrigine (JOURNAVX®) is a novel non-opioid pain medication that was approved in January 2025. Given the well-documented abuse potential of opioids, suzetrigine may become more widely prescribed as an alternative for acute pain management. However, it could still appear in forensic casework as little is understood about its role in polydrug toxicity, comorbidity with pre-existing health conditions, or abuse potential within larger populations. As such, this research aimed to develop the first forensically focused method to detect suzetrigine in blood and urine. Due to its similar physicochemical properties, suzetrigine was seamlessly integrated into a previously validated liquid-liquid extraction method developed for novel dual orexin receptor antagonists (DORAs). This report focuses on the subsequent method development and validation for suzetrigine detection using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The method was validated in accordance with ANSI/ASB 036 for the quantification of suzetrigine in blood and its qualitative identification in urine. A quadratic calibration model with 1/x weighing was utilized (1.0-1000 ng/mL) with quality controls (QCs) at 1.5, 80, 400, and 800 ng/mL. The limit of detection in blood and urine was 0.25 ng/mL, while the limit of quantitation in blood was 1.0 ng/mL. Post-extraction addition at 5 ng/mL and 500 ng/mL yielded matrix effects less than ± 25%, but increased variability at the low concentration in blood was deemed to have no impact on LOD. No carryover or interferences were observed from the internal standard, matrices, or common drugs. Dilution integrity (5X) was acceptable in blood, and processed samples were stable up to 72 hours in the autosampler. In this report we describe a simple extraction for suzetrigine in blood and urine followed by LC-MS/MS analysis. This analytical workflow will be valuable as the use of suzetrigine becomes more prevalent in casework samples.