Determination of Mirtazapine and Desmethyl Mirtazapine inHuman Plasma by a New Validated HPLC Ultraviolet Methodwith a Simple and Reliable Extraction Method: Application toTherapeutic Drug Monitoring Study by 62 Real Patient Plasma

Determination of mirtazapine (mrp) during psychopharmacotherapy in biological fluidsis essential to achieve successful therapy, to avoid toxicity related to drug interactions,genetic variability, and poor compliance. a new, rapid, and sensitive high-performance liquidchromatography method has been developed in human plasma for the determination of mrp andn-desmethylmirtazapine (ndm) that is an active metabolite.the separation was achieved on a reverse-phase c18 250 x 4.6 mm i.d., ods-3 column usingprogrammed gradient elution at 40 °c. 20 mm potassium phosphate buffer (ph 3.9), acetonitrile,and triethylamine (75.0:24.9:0.1, v/v/v) were used as mobile phase a. mobile phase b consistedof absolute acetonitrile. clozapine was used as an internal standard. the method showed linearitywith good determination coefficients (r^2 ≥ 0.9981) for each analyte. intra-day and interday assayprecisions (rsd%) were found less than 3.4 and 2.9 for mrp and ndm, respectively. the intradayand interday accuracy (re%) of the method were calculated between (-2.8) and 5.5. a newextraction method was used in the study and an excellent recovery (average) values for mrp andndm (94.4%, 106.6%, respectively) was obtained. the method was specific and sensitive as thelimit of detection (lod) were 0.17 for mrp and 0.15 ng/ml for ndm.this method was applied properly to plasma samples taken from patients receiving mri (n =62) treated with 15-30 mg / day. the obtained and statistically evaluated plasma mrp and ndmlevels which were 28.6 ± 13.8 and 12.3 ± 6.5 (mean ± sd). the described procedure is relativelysimple, precise, and applicable for routine therapeutic drug monitoring especially in psychiatryclinics and toxicology reference laboratories.