Microdosing, a technique used for about ten years, allows researchers to compare the pharmacokinetics of a very low drug dose with those at a therapeutic dose. About 80% of available microdose pharmacokinetic data scale within a twofold difference of therapeutic doses. The method is expanding beyond pharmacokinetic prediction into areas like studying drug-drug interactions, where volunteers receive a microdose before and after an enzyme-inhibiting or -inducing drug. It also helps obtain early metabolic profiles by administering a 14C-labeled drug and comparing total and unchanged compound concentrations. Microdosing is now being applied to assess drug concentrations in key cell or tissue types, broadening its use in drug development.
A simple and rapid method was developed to estimate administered doses of ayahuasca, supporting further pharmacological and toxicological investigations of ayahuasca exposure.
A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to simultaneously measure the psychedelic drug 5-MeO-DMT and its active metabolite bufotenine in mouse serum. Using a simple protein precipitation and 9-minute run, the assay was linear over a wide concentration range with high precision and accuracy. After injecting mice with 2 mg/kg of 5-MeO-DMT, the systemic exposure to bufotenine was about 1/14 that of the parent drug. Because bufotenine binds the 5-HT2A receptor with roughly ten times higher affinity than 5-MeO-DMT, the metabolite may substantially contribute to the drug's overall pharmacological and toxic effects.