Comparative study of extraction methods from biological material of tricyclic antidepressants: imipramine, clomipramine, amitriptyline

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Introduction. Tricyclic antidepressants (TCAs) are historically the first group of medications used to treat depression. They work by affecting the duration of monoamines presents in the presynaptic cleft in the brain and blocking certain receptors, such as m-cholinergic and alpha-adrenergic. TCAs can cause a toxicological effect and lead to fatal poisoning. This group of drugs is often used among drug addicts, as well as in the criminal environment.

The purpose of the study. Determination of an optimal and effective method for TCAs extraction from biological material using solid-phase (SPE) and liquid-liquid extraction (LLE) for further chemical-toxicological studies.

Materials and methods. The objects of the study were representatives of the TCAs group: imipramine, amitriptyline and clomipramine. Urine was used as a biological material. In the study of SPE method columns produced by Agilent Technologies company were used. These columns contained Evidex and ODS-C18 sorbents. Analutes isolation using LLE were realised according to the one of the most common methods. Analisys were conducted on gas-chromatography with a mass-selective detector (GC/MS).

Results. The method of extraction on a solid sorbent was developed using phosphate buffer with pH 4.8. After using the LLE method, samples with high contamination of co-extracted impurities of biological origin were observed. The error in the results of TCAs extraction using SPE was less than 10%, while the error for the LLE method was 25-35%. A comparison of two different extraction methods was studied using various TCAs concentrations. The advantages of using the ODS-C18 as a sorbent for SPE were determined. Calibration curves were constructed for samples using the SPE method. Limits of detection and quantification for all TCAs were determined.

Conclusions. The advantages of isolating TCAs using the SPE method over the LLE method were revealed.

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作者简介

V. Kulikova

D.I. Mendeleev Russian University of Chemical Technology

编辑信件的主要联系方式.
Email: v.k.kulikova@gmail.com
ORCID iD: 0009-0002-7592-9108
SPIN 代码: 7158-6140

Student

俄罗斯联邦, Miusskaya square, 9, building 1, Moscow, 125047

A. Kirichek

D.I. Mendeleev Russian University of Chemical Technology; 111 Main State Center for Forensic and Criminalistic Examinations of the Ministry of Defense of the Russian Federation

Email: AVK_SUD@mail.ru
ORCID iD: 0009-0006-2202-3168
SPIN 代码: 2844-2985

Senior Lecturer, Department of Expertise in Doping and Drug Control, Forensic Medical Expert, Department of Forensic Chemical Expertise

俄罗斯联邦, Miusskaya square, 9, building 1, Moscow, 125047; Gospitalnaya Ploshchad, d. 3, building 16, Moscow, 105094

A. Shabalina

111 Main State Center for Forensic and Criminalistic Examinations of the Ministry of Defense of the Russian Federation

Email: angelisha81@yandex.ru
ORCID iD: 0009-0001-0383-9464

Ph.D. (Chem.), Head of the Forensic Chemical Examination Department

俄罗斯联邦, Gospitalnaya Ploshchad, d. 3, building 16, Moscow, 105094

N. Raspopova

D.I. Mendeleev Russian University of Chemical Technology

Email: raspopova_nadezhda@inbox.ru
ORCID iD: 0009-0007-6265-1027

Student

俄罗斯联邦, Miusskaya square, 9, building 1, Moscow, 125047

S. Podde

D.I. Mendeleev Russian University of Chemical Technology

Email: comingoutlarry@gmail.com
ORCID iD: 0009-0007-4015-7343

Student

俄罗斯联邦, Miusskaya square, 9, building 1, Moscow, 125047

参考

  1. Aljautdin R.N. Farmakologija. Ultra light: uchebnoe posobie. M.: GJeOTAR-Media. 2012.
  2. Moraczewski J., Aedma K.K. Tricyclic antidepressants. StatPearls Publishing, 2022.
  3. Mashkovskij M.D., Andreeva N.I., Polezhaeva A.I. Farmakologija antidepressantov. M.: Medicina. 1983. T. 11.
  4. Registr lekarstvennyh sredstv Rossii [Jelektronnyj resurs]; https://www.rlsnet.ru/active-substance/klomipramin-157#pharmakologiya.
  5. Ahapkin R.V., Bukreeva N.D., Vazagaeva T.I. i dr. Depressivnyj jepizod. Rekurrentnoe depressivnoe rasstrojstvo. Rossijskoe obshhestvo psihiatrov. 2019.
  6. Afanas'ev V.V. Ostrye otravlenija antidepressantami. Rossijskij Medicinskij Nauchno-Prakticheskij zhurnal. 2000. S. 41.
  7. Kravchenko I.V. Suicidal'nye otravlenija psihotropnymi preparatami. Tihookeanskij medicinskij zhurnal. 2008; 4(34): 51–53.

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2. Fig. 1. Structural formulas: а – Amitriptyline; б – Imipramine; в – Clomipramine

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3. Fig. 2. Solid-phase extraction algorithms

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4. Fig. 3. GC-chromatogram of TCAs extraction by SPE method: а – on the AccuBOND II EVIDEX columns; б – on the AccuBOND II ODS-C18 columns; в – on the SampliQ EVIDEX columns (1 – Amitriptyline; 2 – Imipramine; 3 – Clomipramine)

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5. Fig. 4. GC-chromatogram of TCAs extraction by LLE method (1 – Amitriptyline; 2 – Imipramine; 3 – Clomipramine)

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6. Fig. 5. Calibration curve for the quantitative analysis of amitriptyline using columns: а – AccuBond II ODS-C18 (r2=0,98); б – AccuBond II EVIDEX (r2=0,97); в – SampliQ EVIDEX (r2=0,96)

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7. Fig. 6. Calibration curve for the quantitative analysis of imipramine using columns: а –AccuBond II ODS-C18 (r2=0,99); б – AccuBond II EVIDEX (r2=0,98); в – SampliQ EVIDEX (r2=0,99)

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8. Fig 7. Calibration curve for the quantitative analysis of clomipramine using columns: а – AccuBond II ODS-C18 (r2=0,99); б – AccuBond II EVIDEX (r2=0,98); в – SampliQ EVIDEX (r2=0,98)

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