Determination of Mirtazapine and Desmethyl Mirtazapine in Human Plasma by a New Validated HPLC Ultraviolet Method with a Simple and Reliable Extraction Method: Application to Therapeutic Drug Monitoring Study by 62 Real Patient Plasma
IRANIAN JOURNAL OF PHARMACEUTICAL RESEARCH, sa.1, ss.18-30, 2020 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Basım Tarihi: 2020
- Doi Numarası: 10.22037/ijpr.2019.14599.12519
- Dergi Adı: IRANIAN JOURNAL OF PHARMACEUTICAL RESEARCH
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, EMBASE, International Pharmaceutical Abstracts, Veterinary Science Database
- Sayfa Sayıları: ss.18-30
- Anahtar Kelimeler: Mirtazapine, N-desmethylmirtazapine, Plasma, HPLC-UV, Therapeutic drug monitoring, Validation, PERFORMANCE LIQUID-CHROMATOGRAPHY, DEMETHYL METABOLITE, ACTIVE METABOLITES, PHARMACOKINETICS, OVERDOSE, SAFETY, ANTIDEPRESSANTS, REMERON(R), SEPARATION
- Ankara Üniversitesi Adresli: Evet
Özet
Determination of mirtazapine (MRP) during psychopharmacotherapy in biological fluids is essential to achieve successful therapy, to avoid toxicity related to drug interactions, genetic variability, and poor compliance. A new, rapid, and sensitive high-performance liquid chromatography method has been developed in human plasma for the determination of MRP and N-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 using programmed gradient elution at 40 degrees 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 consisted of absolute acetonitrile. Clozapine was used as an internal standard The method showed linearity with good determination coefficients (r(2)>= 0.9981) for each analyte. Intra-day and interday assay precisions (RSD%) were found less than 3.4 and 2.9 for MRP and NDM, respectively. The intraday and interday accuracy (RE%) of the method were calculated between (-2.8) and 5.5. A new extraction method was used in the study and an excellent recovery (average) values for MRP and NDM (94.4%, 106.6%, respectively) was obtained. The method was specific and sensitive as the limit 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 NDM levels which were 28.6 +/- 13.8 and 12.3 +/- 6.5 (mean +/- SD). The described procedure is relatively simple, precise, and applicable for routine therapeutic drug monitoring especially in psychiatry clinics and toxicology reference laboratories.