Quantification of Tricyclic Antidepressants Using UPLC-MS/MS

Abstract

Depression is a psychiatric condition that affects about 120 million people worldwide and can interfere with independence and productivity in essentially all aspects of daily life. Depression is also associated with risk of self-harm, and ultimately suicide. Antidepressant medications are widely used to treat symptoms of depression. While there are several classes of antidepressants, therapeutic drug management (TDM) is most common for the tricyclic antidepressants (TCAs). TDM of TCAs is important due to wide inter-individual variability in pharmacokinetics, production of active metabolites, and a high risk of drug-drug interactions. In addition, TDM of some TCAs can be used to optimize dose, wherein concentration relationships are recognized for both therapeutic response and potentially life-threatening toxicity. In many clinical scenarios, TDM of TCAs is accomplished by currently available point of care or automated immunoassays that provide a "total" TCA concentration. However, these assays may not be adequately specific to meet the needs of all clinical scenarios, and hence, chromatographic separation and quantification of individual TCA parent drugs and active metabolites that may contribute to the "total" TCA concentration is sometimes required. This chapter describes an analytical method designed to detect and/or quantify clinically significant concentrations of nine TCAs (amitriptyline, nortriptyline, imipramine, desipramine, doxepin, nordoxepin, protriptyline, clomipramine, and norclomipramine) in serum or plasma, using ultra pressure liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The sample preparation employs a rapid protein precipitation with 50:50 MeOH:acetonitrile, high speed centrifugation, and injection of 5 μL of supernatant onto the instrument, with a 5 min run-time.

Highly sensitive LC–MS/MS method to estimate doxepin and its metabolite nordoxepin in human plasma for a bioequivalence study

“…Therapeutic drug monitoring for Dox is essential due to wide inter-individual variability observed in the pharmacokinetics and in the production of active metabolite. This can help to optimize dose and thus minimize potentially life-threatening toxicity [8].…”

“…Moreover, they have limited sensitivity (lower limit of quantitation) in the range of 0.25–100 ng/mL for both the analytes. Further, assay methods for the determination of Dox together with several TCAs, other antidepressants and antipsychotic drugs using capillary electrophoresis [14], HPLC [15], [16], [17], [18], [19], gas chromatography–mass spectrometry (GC–MS) [20], LC–MS/MS [21], [22] and ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) [8], [23], [24], [25] in biological samples have also been reported.…”

A Simple, Rapid and Reliable Method to Determine Imipramine and Desipramine in Mouse Serum Using Ultra-High-Performance Liquid Chromatography–Quadrupole-Time-of-Flight Mass Spectrometry

“…Imipramine is metabolized in the liver primarily to desipramine, which also has antidepressant activity (11) by inhibiting the reuptake of norepinephrine and serotonin (12). TDM of imipramine and desipramine is essential due to wide interindividual variability in pharmacokinetics, production of active metabolites and a high risk of drug-drug interactions (13).…”