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In this context, both qualitative and quantitative determination of bioactive peptides in biological fluids\/tissues and their effect on endogenous factors (e.g. hormones) are of great importance. A mass spectrometry\u2010based approach was developed and applied towards the measurement of leuprolide, a peptide drug for the treatment of prostate cancer, in mouse plasma. High\u2010pressure liquid chromatography coupled to a hybrid quadrupole linear ion trap (QqLIT) mass spectrometer, a platform that combines the benefits of triple QqLIT instruments, was employed for the study. Using the described methodology, we established that picomolar concentrations of leuprolide could be measured in mouse plasma (limit of quantification of 0.1 ng\/ml). In order to optimize pharmacokinetic properties of analogs of leuprolide, a facile <jats:italic>in vivo<\/jats:italic> mouse model was developed and leuprolide concentrations were determined in mouse plasma following intraperitoneal administration. In the same animal model, we demonstrated the versatility of the described MS\u2010based approach by the determination of plasma concentrations of testosterone, an established biomarker for the treatment of prostate cancer. Following dosing with leuprolide, circulating testosterone was increased significantly in comparison to vehicle\u2010treated mice. Finally, <jats:italic>in vitro<\/jats:italic> metabolism of leuprolide was evaluated by incubation of leuprolide with mouse kidney membranes, followed by identification of major metabolites by MS. Such studies provide the framework for future evaluation of novel leuprolide analogs with potential therapeutic advantages. Copyright \u00a9 2008 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/jms.1416","type":"journal-article","created":{"date-parts":[[2008,4,28]],"date-time":"2008-04-28T07:19:08Z","timestamp":1209367148000},"page":"1381-1392","source":"Crossref","is-referenced-by-count":32,"title":["<i>In vivo<\/i> evaluation and <i>in vitro<\/i> metabolism of leuprolide in mice\u2014mass spectrometry\u2010based biomarker measurement for efficacy and toxicity"],"prefix":"10.1002","volume":"43","author":[{"given":"Zacharias 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