Development of conditions for the isolation of mirtazapine from blood and urine
DOI:
https://doi.org/10.11603/2312-0967.2026.1.16071Keywords:
mirtazapine, biological fluids, blood, urine, isolation, UV spectrophotometryAbstract
The aim of the work. To develop optimal conditions for isolating mirtazapine from model blood and urine samples based on the use of liquid-liquid extraction.
Material and Methods. When performing the research, model mixtures of biological fluids of volunteers were used, to which mirtazapine solutions were added. Isolation of the studied antidepressant from blood and urine samples was carried out by the method of liquid-liquid extraction with chloroform from a pre-alkaline medium at pH 11 and with the addition of sodium sulphate as a salting-out agent. To remove endogenous components from biological fluids, they were previously extracted with diethyl ether from an acidic medium at pH 1. During blood sample preparation, the formed elements of the biofluid were separated by precipitation using 2% solution of trichloroacetic acid. Quantitative determination of the content of mirtazapine in the obtained extracts was carried out by the UV-spectrophotometric method after additional purification using TLC.
Results and Discussion. Mirtazapine was detected in the obtained extracts from blood and urine samples by light absorption spectra in the UV region, which coincided in nature with the standard solution of the drug in 0.1 M hydrochloric acid solution and had light absorption maxima at wavelengths of 253±2, 273±2 and 316±2 nm. For the quantitative determination of the studied antidepressant in the extracts, the equation of the calibration curve y=0.0272x was used, which was linear within the drug concentration range of 1.5–45.0 μg/ml. The degree of isolation of mirtazapine from the biological fluids was 36.4±3.5% (blood) and 78.7±3.4% (urine).
Conclusions. Effective methods for isolating mirtazapine from the model blood and urine samples based on liquid-liquid extraction in the presence of sodium sulphate as a salting-out agent have been proposed. The possibility of using the UV spectrophotometric method for the detection and quantitative determination of mirtazapine in the biological fluids has been shown, which is confirmed by the given validation parameters and in accordance with the probable content of the studied drug in human biological fluids in the case of lethal intoxications. The obtained results of experimental studies can be used in conducting forensic toxicological examinations in cases of poisoning with antidepressants.
References
Spasovska Trajanovska A, Pereska Z, Mitic Z. Antidepressant Therapy and Depression Disorder. Pril. Makedon. Akad. Nauk. Umet. Odd. Med. Nauki. 2025;46(2):75-81. https://doi.org/10.2478/prilozi-2025-0016 DOI: https://doi.org/10.2478/prilozi-2025-0016
Xie S, Liu Y. Efficacy of mirtazapine combined with escitalopram in the treatment of sleep disorders in patients with depression. Minerva Surg. 2024; 79(2):241-3. https://doi.org/10.23736/S2724-5691.21.09325-4 DOI: https://doi.org/10.23736/S2724-5691.21.09325-4
H. Yamamoto H, Takayasu T, Ishida Y, Nosaka M, Hata S, Kuninaka Y, et al. A case of complex suicide due to acute nicotine intoxication caused by cigarette ingestion. Int. J. Legal Med. 2019; 134(3):997-1002. https://doi.org/10.1007/s00414-019-02228-5 DOI: https://doi.org/10.1007/s00414-019-02228-5
Strano-Rossi S, Mestria S, Bolino G, Polacco P, Grassi S, Oliva O, et al. Scopolamine fatal outcome in an inmate after buscopan® smoking. Int. J. Legal Med. 2021; 135(4):1455-60. https://doi.org/10.1007/s00414-021-02583-2 DOI: https://doi.org/10.1007/s00414-021-02583-2
Nedahl M, Johansen SS, Linnet K. Reference Brain/Blood Concentrations of Citalopram, Duloxetine, Mirtazapine and Sertraline. J. Anal. Toxicol. 2017;42(3):149-56. https://doi.org/10.1093/jat/bkx098 DOI: https://doi.org/10.1093/jat/bkx098
Dural E, Baskak NS, Özcan H, Kır Y, Başkak B, Süzen HS. 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. Iran. J. Pharm. Res. 2020;19(10):18-30. https://doi.org/10.22037/ijpr.2019.14599.12519
Yan QT, Chen MC, Hsieh MM. Ultrasensitive analysis of mirtazapine and its metabolites enantiomers in body fluids using ultrasound-enhanced and surfactant-assisted dispersive liquid–liquid microextraction followed by polymer-mediated stacking in capillary electrophoresis. J. Chromatogr. A. 2022; 463328 p. https://doi.org/10.1016/j.chroma.2022.463328 DOI: https://doi.org/10.1016/j.chroma.2022.463328
Zhong J, Liu X, Chen L, Li K, Hu Q, Wu K, et al. Simultaneous separation and determination of several chiral antidepressants and their enantiomers in wastewater by online heart-cutting two-dimensional liquid chromatography. Ecotoxicol. Environ. Saf. 2023;263:115302. https://doi.org/10.1016/j.ecoenv.2023.115302 DOI: https://doi.org/10.1016/j.ecoenv.2023.115302
El‐Habab RGG, Saad S, Aly FA. A Novel Simple First‐Derivative Synchronous Spectrofluorimetric Approach for Dual Estimation of Duloxetine and Mirtazapine in Dosage Forms and Biological Human Plasma. Lumin. 2025;40(11):e70345. https://doi.org/10.1002/bio.70345 DOI: https://doi.org/10.1002/bio.70345
Savchenko MA, Chubenko VO. Nastanova shchodo provedennia sudovo–toksykolohichnykh doslidzhen [Guidelines for conducting forensic toxicological studies]. Kyiv, 2024. 58 s. [in Ukrainian]. Available from: https://repo.knmu.edu.ua/server/api/core/bitstreams/1def16b9-a318-4134-b3ec-44986ae60747/content
ICH Harmonised Guideline. Validation of Analytical Procedures Q2(R2) [Electronic resource]. 2022. 39 p. Available from: ich-guideline-q2r2-validation-analytical-procedures-step-2b_en.pdf
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Accepted 2026-03-31
Published 2026-03-31
