An in-depth Analysis on Four Classes of Antidepressants Quantification from Human Serum using LC-MS/MS

Abstract

Abstract 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 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 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 5-different classes of the 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 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 we have 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 post-partum depression for large number of patient samples using automation.