A Simple and Sensitive Method for the Determination of Tranylcypromine in Plasma with LC-MS/MS

Objectives: Therapeutic drug monitoring (TDM) of psychotropic drugs is a useful tool to optimize drug therapy. Analytical methods are well established for most common drugs. Usually tranylcypromine does not belong to this group. TDM is limited to few cases per year, e.g.lack of compliance, interaction with co-medications and possible intoxication. With the concept of a simple protein precipitation and sensitive LC-MS/MS detection it is possible to obtain a method, readily available for determination of rarely requested drugs like tranylcypromine.

Material and Methods: After protein precipitation by addition of acetonitrile/methanol with internal standard baclofen, dilution of the supernatant and separation on a high speed monolytic C18 column (Chromolith C18, 50×4.6mm; Merck) with mobile phase of acetonitrile/5mM acetic acid, pH 3.9 with ammonia (10:90) and flow rate of 1ml/min, selective positive ion fragments were generated and detected after electrospray ionization in the API 4000 triple-quadrupol mass spectrometer (Applied Biosystems) in MRM mode.

Results: Retention time of tranylcypromine and the internal standard were 1.4 and 1.6min, respectively. Parent and daughter ions of tranlycypromine were 134.2/117.0 m/z (quantifier) and 134.2/91.0 m/z (qualifier). Parent and daugther ions for the internal standard were 213.9/151.0 m/z. A detection limit of 0.5 ng/ml and an intra-assay coefficient of variation of 5.4% of spiked plasma with 10 ng/ml tranylcypromine were found. Linearity of spiked plasma was tested in the range of 1–100 ng/ml. Injection interval of isokratic HPLC was 2.5min.

Conclusions: It is demonstrated that the LC-MS/MS method for tranylcypromine determination is simple and sensitive enough for routine analysis of this drug. Even when only rarely requested, it is possible to insert this method to an existing set of frequent performed TDM.