An in-depth analysis of four classes of antidepressants quantification from human serum using LC–MS/MS

Depression is a growing global crisis, with females at a higher rate of diagnosis than males. While the percentage of patients on prescribed antidepressants have tripled over the last two decades, we are still at a crossroad where the discrepancy lies between finding a drug to suit a patient and monitoring the abundance of it in the body to prevent unwanted side effects. Liquid Chromatography tandem mass spectrometry (LC-MS/MS) has garnered the attention of clinicians as a technique to accurately monitor therapeutic drugs in human serum with high specificity and accuracy. This may be a potential solution, but the challenge persists in the realm of sample preparation, where a method is automatable. We have developed and validated an LC-MS/MS-based assay for simultaneous quantification of 4 different classes of commonly prescribed antidepressants in women that is automated using a JANUS G3 Robotic Liquid Handler. Our method utilizes a simple sample preparation technique, utilizing only 20 μL of a serum sample, to accurately measure Bupropion, Citalopram, Desipramine, Imipramine, Olanzapine, Sertraline and Vilazodone across a range of 1.0 to 230 ng/mL. Our method exhibits a linearity of R2 ≥ 0.99 when detected in MRM mode and % CV of ≤ 20% for all analytes across the board. In addition, we have designed a prototype that can be utilized at a clinical mass spectrometry lab and assessed the long-term use of this prototype using an accelerated stability study. Overall, our developed method has the potential to be translated to clinical settings to monitor postpartum depression for a large number of patient samples using automation.