An original method based on the use of high-performance liquid chromatography with both coulometric and diode array detection has been developed for the therapeutic drug monitoring of patients with bipolar disorders being treated with olanzapine and lamotrigine. Chromatographic separation was achieved on a reversed-phase C8 column (150 × 4.6 mm internal diameter, 5 μm) using a mobile phase composed of methanol (27%) and a 50.0 mmol/L, pH 3.5 phosphate buffer (73%). For the analysis of olanzapine and its main metabolite, N-desmethylolanzapine, a coulometric detector was used, with electrode 1 set at -200 mV and electrode 2 at +500 mV. Lamotrigine was determined using a diode array detection at 220 nm. The two detectors were connected in series. For the analysis of biological samples, a clean-up procedure was implemented by means of solid-phase extraction using phenyl cartridges and eluting the analytes with methanol; only a small volume of plasma (150 μL) was needed to analyze both olanzapine and lamotrigine. Linear responses were obtained between 0.1 and 50.0 ng mL−1 for olanzapine, 0.1 and 25.0 ng mL−1 for N-desmethylolanzapine, and between 0.25 and 10.0 μg mL−1 for lamotrigine. The extraction yield values were always higher than 90% for all the analytes, with precision (expressed as relative standard deviation values) lower than 3.4%. The method was applied successfully to some human plasma samples drawn from bipolar patients undergoing combined therapy with the two drugs. Satisfactory values for accuracy were obtained, with mean recovery higher than 91%. Thus, the method appears suitable for the investigation of the chemical-clinical correlations in patients receiving therapy with olanzapine and lamotrigine.
From the *Pharmaco-Toxicological Analysis Laboratory, Department of Pharmaceutical Sciences, Faculty of Pharmacy, Alma Mater Studiorum, University of Bologna, Bologna, Italy; †“Lucio Bini” Center, Rome, Italy; ‡Hospital “Sant'Andrea,” University “La Sapienza,” Rome, Italy; and §Department of Neurosciences, Psychiatric Division, Faculty of Medicine and Surgery, University of Parma, Parma, Italy.
Received for publication March 25, 2007; accepted September 1, 2007.
Supported by RFO (ex-60%) grant from MIUR (Ministero dell'Istruzione, dell'Università e della Ricerca, Italy).
Reprints: Prof. Maria Augusta Raggi, Department of Pharmaceutical Sciences, Via Belmeloro 6, 40126 Bologna, Italy (e-mail: email@example.com).