By employing quantitative LC-MS/MS to quantify plasma levels of caffeine, paraxanthine, trigonelline, piperine, and sitosteryl hexoside, our study delineates differences across healthy controls and PD subgroups, including those with LRRK2 and GBA1 mutations, while exploring temporal dynamics and correlations with disease severity. The gene discussed is LRRK2; the disease is Parkinson disease.