THE ISOLATION OF TRAZODONE FROM THE BIOLOGICAL FLUIDS

Authors

DOI:

https://doi.org/10.11603/2312-0967.2025.1.15167

Keywords:

Trazodone, biological fluids, isolation, TLC, UV spectrophotometry

Abstract

The aim of the work: to optimize the method for Trazodone isolation from blood and urine by liquid-liquid extraction technique.

Materials and Methods. The study was carried out with model samples of human biofluids spiked with Trazodone. The antidepressant was isolated from the blood and urine by the liquid-liquid extraction technique with methylene chloride from the alkaline aqueous medium at pH 9 at the presence of ammonium sulphate as a salting-out agent. The biological impurities were previously removed by extraction with diethyl ether from the acidic medium at pH 1. The erythrocyte mass of the blood was pre-precipitated with the help of 5% trichloroacetic acid. The resulting extracts were additionally purified using TLC technique. Quantitative determination of Trazodone in the extracts was carried out with the help of UV spectrophotometry.

Results and Discussion. Trazodone was detected in the biological extracts by UV spectra which coincided with standard methanol solution of the analyte and had the principal peak at wavelength of 251±2 nm. Quantitative determination of the drug in the extracts was performed with the help of calibration curve described by the equation y=(0.0230±1×10-4x, which showed linearity in the range of analyte concentration 2.5–50.0 μg/mL. Recovery values of the developed sample preparation methods were determined in the range of the drug concentrations of 10–50 µg/mL and 4–20 µg/mL for blood and urine respectively.

Conclusions. Effective methods for Trazodone isolation from blood and urine using liquid-liquid extraction in the presence of ammonium sulphate as a salting-out agent have been developed. It has been established that liquid-liquid extraction in the presence of electrolytes provided more effective Trazodone isolation from the biological fluids than under optimized conditions without salting-out agents. The recovery of the optimized methods was 52±3% for blood and 91±3% for urine that provided sufficient extraction yield of the antidepressant for its determination within the level of the expected acute concentrations in the biological fluids. The ability of UV spectrophotometry as an analytical method for determination of Trazodone in biological fluids has been proven by a range of validation parameters. The obtained results can be used for forensic toxicological examinations in cases of acute and fatal intoxications by antidepressants.

Author Biographies

S. V. Baiurka, National Pharmaceutical University of the Ministry of Health of Ukraine

DSc (Pharmacy), Professor, Department of Pharmaceutical Chemistry

S. A. Karpushyna, Uman National University of Horticulture

PhD (Chemistry), Associate Professor, Department of Biology

References

Yajnik K, Thakar N, Chovatiya H, Desai S. Trazodone-Associated Extrapyramidal Syndrome: a Case Report and Review of Literature. Ann Indian Acad Neurol. 2024;27(1):85-7. DOI: 10.4103/aian.aian_774_23 DOI: https://doi.org/10.4103/aian.aian_774_23

Yilbaş B. Restless Legs Syndrome Due to the Use of Trazodone: a Case Report. Turk. Psikiyatri Derg. 2022;33(1):70-2. DOI: 10.5080/u25787 DOI: https://doi.org/10.5080/u25787

Khouzam HR. A review of trazodone use in psychiatric and medical conditions. Postgrad Med. 2017;129(1):140-8. DOI: 10.1080/00325481.2017.1249265

Fagiolini A, Amodeo G, Goracci A, Blardi P. Trazodone Contramid® nella pratica clinica: strategie per la personalizzazione dell’intervento antidepressivo [Trazodone Contramid® in clinical practice: personalizing antidepressant intervention]. Riv Psichiatr. 2016;51(4):123-8. DOI: 10.1708/2342.25112

Pereira AT., Mota D, Ribeiro L, Rodrigues JD. Trazodone-induced delirium: case report. Rev Colomb Psiquiatr. (Engl Ed). 2020;49(3):199-201. DOI: 10.1016/j.rcp.2018.10.006 DOI: https://doi.org/10.1016/j.rcpeng.2018.10.013

Wichniak A, Wierzbicka AE, Jarema M. Treatment of insomnia-effect of trazodone and hypnotics on sleep. Psychiatr Pol. 2021;55(4):743-55. DOI: 10.12740/PP/125650 DOI: https://doi.org/10.12740/PP/125650

Kanamori T, Kaneko Y, Yamada K, Suzuki M. Successful Combination Therapy of Trazodone and Fluvoxamine for Pica in Alzheimer's Disease: a Case Report. Front Psychiatry. 2021;12:704847. DOI: 10.3389/fpsyt.2021.704847 DOI: https://doi.org/10.3389/fpsyt.2021.704847

He X, Lang Q, Pei ZM, Yan HY. Successful treatment of auto-trilevel positive airway pressure plus trazodone for obstructive sleep apnea complicated by anxiety disorder: a case report. J Int Med Res. 2023;51(8):3000605231193924. DOI: 10.1177/03000605231193924 DOI: https://doi.org/10.1177/03000605231193924

Rosso G, Benatti B, Pettorruso M, Sampogna G, Tomasetti C. Case report: Personalizing the use of trazodone in real-world patients: a study of three cases of depression with comorbidities. Front Psychiatry. 2024;15:1362221. DOI: 10.3389/fpsyt.2024.1362221 DOI: https://doi.org/10.3389/fpsyt.2024.1362221

Khouzam HR. A review of trazodone use in psychiatric and medical conditions. Postgrad Med. 2017;129(1):140-8. DOI: 10.1080/00325481.2017.1249265 DOI: https://doi.org/10.1080/00325481.2017.1249265

Ali HT, Soliman ZA, Aborigiba F, Caprara ALF, Rissardo JP. Trazodone-induced parkinsonism in a middle-aged male: a case report. Afr Health Sci. 2024;24(1):206-12. DOI: 10.4314/ahs.v24i1.25 DOI: https://doi.org/10.4314/ahs.v24i1.25

Skarmeta NP, Katzmann GC, Valdés C, Gaedechens D, Montini FC. Tardive Oromandibular Dystonia Induced by Trazodone: a Clinical Case and Management from the Perspective of the Dental Specialist. Toxins (Basel). 2022;14(10):680. DOI: 10.3390/toxins14100680 DOI: https://doi.org/10.3390/toxins14100680

Fernandes NF, Martin RR, Schenker S. Trazodone-induced hepatotoxicity: a case report with comments on drug-induced hepatotoxicity. Am J Gastroenterol. 2000;95(2):532-5. DOI: 10.1111/j.1572-0241.2000.t01-1-01780.x DOI: https://doi.org/10.1111/j.1572-0241.2000.t01-1-01780.x

Mannocchi G, Tittarelli R, Pantano F, Vernich F, Pallocci M, Passalacqua P, et al. Forensic Aspects of a Fatal Intoxication Involving Acetaminophen, Citalopram and Trazodone: a Case Report. Toxics. 2022;10(8):486. DOI: 10.3390/toxics10080486 DOI: https://doi.org/10.3390/toxics10080486

Warnant A, Gerard L, Haufroid V, Hantson P. Coma Reversal After Intravenous Lipid Emulsion Therapy in a Trazodone-Poisoned Patient. Clin Neuropharmacol. 2020;43(1):31-3. DOI: 10.1097/WNF.0000000000000376 DOI: https://doi.org/10.1097/WNF.0000000000000376

Potměšil P, Kostýlková L, Kopeček M. Increased amisulpride serum concentration in a patient treated with concomitant pregabalin and trazodone: a case report. Ther Adv Psychopharmacol. 2022;12:20451253221136754. DOI: 10.1177/20451253221136754 DOI: https://doi.org/10.1177/20451253221136754

Knych HK, Mama KR, Steffey EP, Stanley SD, Kass PH. Pharmacokinetics and selected pharmacodynamics of trazodone following intravenous and oral administration to horses undergoing fitness training. Am J Vet Res. 2017;78(10):1182-92. DOI: 10.2460/ajvr.78.10.1182 DOI: https://doi.org/10.2460/ajvr.78.10.1182

Ruggieri A, Picollo R, Del Vecchio A, Calisti F, Dragone P, Comandini A, et al. Investigations on dose proportionality and drug-drug interaction for a fixed-dose combination of trazodone and gabapentin. Int J Clin Pharmacol Ther. 2021;59(1):71-86. DOI: 10.5414/CP203845 DOI: https://doi.org/10.5414/CP203845

Ding J, Zhang Y, Cui X, Zhao C, Zhang S. Development of a Novel Analytical Method for Determining Trazodone in Human Plasma by Liquid Chromatography Coupled with Mass Spectrometry Coupled with Automatic 2-Dimensional Liquid Chromatograph-Mass Spectrometer Coupler 9500 and Its Application to Therapeutic Drug Monitoring. Ther Drug Monit. 2022;44(3):465-73. DOI: 10.1097/FTD.0000000000000921 DOI: https://doi.org/10.1097/FTD.0000000000000921

Olivieri S, Bovi G, Petrucci V, Alfieri A, Oggianu L, Picollo R, et al. Juvenile rat and pediatric trazodone studies: how to gain extra sensitivity to overcome bioanalytical challenges. Bioanalysis. 2019;11(1):21-2. DOI: 10.4155/bio-2018-0236 DOI: https://doi.org/10.4155/bio-2018-0236

Ragab GH, Bahgat EA. Development of HPLC method coupled with fluorescence detection for simultaneous determination of donepezil HCl and trazodone HCl in spiked human plasma and tablets dosage forms. Ann Pharm Fr. 2019; 77(4): 286-94. DOI: 10.1016/j.pharma.2019.02.003 DOI: https://doi.org/10.1016/j.pharma.2019.02.003

Li-Bo D, Rong-Hua Z, Huan-De L, Feng W, Ping-Fei F, Jiang L. Quantitative analysis of trazodone in human plasma by using HPLC-fluorescence detector coupled with strong cation exchange chromatographic column: application to a pharmacokinetic study in Chinese healthy volunteers. J. Chromatogr B Analyt Technol Biomed Life Sci. 2014;944:43-48. DOI: 10.1016/j.jchromb.2013.11.013 DOI: https://doi.org/10.1016/j.jchromb.2013.11.013

Kashi F, Ebrahimzadeh H, Nejabati F. Development and characterization of a non-enzymatic electrochemical biosensor for rapid determination of sorbent-based extracted trazodone and doxepin in complicated samples. Anal Chim Acta. 2024;1317:342902. DOI: 10.1016/j.aca.2024.342902 DOI: https://doi.org/10.1016/j.aca.2024.342902

De Boeck M, Dubrulle L, Dehaen W, Tytgat J, Cuypers E. Fast and easy extraction of antidepressants from whole blood using ionic liquids as extraction solvent. Talanta. 2018;180:292-99. DOI: 10.1016/j.talanta.2017.12.044 DOI: https://doi.org/10.1016/j.talanta.2017.12.044

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

Karpushyna SA, Baiurka SV, Merzlikin SI. Laboratory toxicological diagnosis of trazodone intoxications. Clinical pharmacy. 2021;25(1):57-62. Available from: http://cphj.nuph.edu.ua/article/view/223921 DOI: https://doi.org/10.24959/cphj.21.1544

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Published

2025-03-31

How to Cite

Baiurka, S. V., & Karpushyna, S. A. (2025). THE ISOLATION OF TRAZODONE FROM THE BIOLOGICAL FLUIDS. Pharmaceutical Review Farmacevtičnij časopis, (1), 32–38. https://doi.org/10.11603/2312-0967.2025.1.15167

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Section

Analysis of drugs