Progress in pretreatment of methadone: an update since 2015

Methadone, a µ-opioid receptor agonist, is widely used in pain-relieving and treating opioid dependence. If not strictly controlled, as an opioid substitute, it can lead to abuse and cause more severe withdrawal responses than heroin. Also, overdose or abuse of this drug in clinical use may provide severe side effects such as apnea, circulatory collapse, cardiac arrest, and even death. For these reasons, simple, rapid, and efficient methods have been developed for the pretreatment of methadone. This review presents a comprehensive conclusion of the pretreatment methods used for methadone in various sample matrices, focusing on the developments since 2015. Traditionally used pretreatment methods like solid-phase extraction and liquid-liquid extraction are discussed and newly developed methods like solid-phase microextraction and liquid-liquid microextraction along with new materials applied are focused.