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.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
National Institute of Mental Health (2010) Just over half of Americans diagnosed with major depression receive care. http://www.nimh.nih.gov/science-news/2010/just-over-half-of-americans-diagnosed-with-major-depression-receive-care.shtml
Kessler RC, McGonagle KA, Zhao S et al (1994) Lifetime and 12-month prevalence of DSM-III R psychiatric disorders in the United States. Results from the National Comorbidity Study. Arch Gen Psychiatry 51:8–19
Masand PS (2003) Tolerability and adherence issues in antidepressant therapy. Clin Therapeutics 25:2289–2304
Joffe R, Sokolov S, Streiner D (1993) Antidepressant treatment of depression: a meta-analysis. Can J Psychiatry 41:613–616
Owens MJ, Morgan WN, Plott SJ, Nemeroff CB (1997) Neurotransmitter receptor and transporter binding profile of antidepressants and their metabolites. J Pharmacol Exp Ther 283:1305–1322
Perry PJ, Zeilman C, Arndt S (1994) Tricyclic antidepressant concentrations in plasma: an estimate of their sensitivity and specificity as a predictor of response. J Clin Psychopharmacol 14:230–240
Williams RB Jr, Sherter C (1971) Cardiac complications of tricyclic antidepressant therapy. Ann Intern Med 74:395–398
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Johnson-Davis, K.L., Juenke, J.M., Davis, R., McMillin, G.A. (2012). Quantification of Tricyclic Antidepressants Using UPLC-MS/MS. In: Langman, L., Snozek, C. (eds) LC-MS in Drug Analysis. Methods in Molecular Biology, vol 902. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61779-934-1_16
Download citation
DOI: https://doi.org/10.1007/978-1-61779-934-1_16
Published:
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-61779-933-4
Online ISBN: 978-1-61779-934-1
eBook Packages: Springer Protocols