Validation of a microsampling-compatible liquid–liquid extraction method for cannabinoid quantitation in 50 µL of whole blood using liquid chromatography–mass spectrometry

Abstract Recently developed dried blood analysis methods for cannabinoid quantitation utilize small blood volumes, making them microsampling-compatible, but are limited by hematocrit-related bias for dried blood spots (DBSs) and higher consumable costs for volumetric absorptive microsampling (VAMS®). To address these issues, we developed a highly sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method capable of quantifying cannabinoids in 50 µL of liquid whole blood, providing a practical microsampling alternative to dried blood approaches. Using liquid–liquid extraction (LLE) with sodium hydroxide alkalinization