Advances in Chlorpromazine Detection Technologies: A Review
DOI:
https://doi.org/10.6911/WSRJ.202604_12(4).0004Keywords:
Chlorpromazine; chromatography-mass spectrometry; electrochemical sensing; immunoassay; rapid detection; simultaneous multi-analyte detection.Abstract
Chlorpromazine (CPZ) is a representative phenothiazine antipsychotic that needs to be analytically assessed reliably in clinionmental fate and transformation research. Conventional techniques such as high-performance liquid chromatcal therapeutic monitoring of drugs, residue analysis of animal-derived foods, forensic toxicology, and envirography, gas chromatography and enzyme-linked immunosorbent assay have traditionally been employed to analyze CPZ but remain limited in ultra-trace detection, scalability to complex matrices, swift on site screening, and multiplexed multi-analyte analysis. Over the past few years, chromatographic-mass spectrometry-based methodologies, spectroscopic and nano-optical assays, electrochemical sensors, new immunoassays and biosensors have grown at a fast pace offering new lines of analysis of the CPZ quantitation in plasma, oral fluid, tissue and animal samples, food, and environmental samples. The current review presents the advances in CPZ detection technologies in the last few years focusing on selected articles published between 2015 and 2025 on the chromatographic and chromatography-mass spectrometry methods, rapid testing approaches, and up-and-coming sensing technologies. Also considered are sample preparation, method optimization, technical comparison, applications, and future trends. On the whole, chromatography-mass spectrometry remains the most popular platform in confirmatory analysis and high-precision quantification, whereas fast optical, electrochemical, and immunochemical techniques are also promising in field screening, microsample analysis, and point-of-care testing.
Downloads
References
[1] Pujadas M, Pichini S, Civit E, Santamariña E, Perez K, de la Torre R. A simple and reliable procedure for the determination of psychoactive drugs in oral fluid by gas chromatography-mass spectrometry. Journal of Pharmaceutical and Biomedical Analysis. 2007;44(2):594–601. DOI: 10.1016/j.jpba.2007.02.022.
[2] da Fonseca BM, Moreno IED, Barroso M, et al. Determination of seven selected antipsychotic drugs in human plasma using microextraction in packed sorbent and gas chromatography-tandem mass spectrometry. Analytical and Bioanalytical Chemistry. 2013;405(12):3953–3963. DOI: 10.1007/s00216-012-6695-y.
[3] Caramelo D, Rosado T, Oliveira V, et al. Determination of antipsychotic drugs in oral fluid using dried saliva spots by gas chromatography-tandem mass spectrometry. Analytical and Bioanalytical Chemistry. 2019;411(23):6141–6153. DOI: 10.1007/s00216-019-02005-8.
[4] Kul A, Sagirli O. A new method for the therapeutic drug monitoring of chlorpromazine in plasma by gas chromatography-mass spectrometry using dispersive liquid-liquid microextraction. Bioanalysis. 2023;15(22):1343–1354. DOI: 10.4155/bio-2023-0176.
[5] Orfanidis A, Krokos A, Mastrogianni O, Gika H, Raikos N, Theodoridis G. Development and Validation of a Single Step GC/MS Method for the Determination of 41 Drugs and Drugs of Abuse in Postmortem Blood. Forensic Sciences. 2022;2(3):473–491. DOI: 10.3390/forensicsci2030035.
[6] Borges NC, Rezende VM, Santana JM, et al. Chlorpromazine quantification in human plasma by UPLC-electrospray ionization tandem mass spectrometry: Application to a comparative pharmacokinetic study. Journal of Chromatography B. 2011;879(31):3728–3734. DOI: 10.1016/j.jchromb.2011.10.020.
[7] Khelfi A, Azzouz M, Abtroun R, Reggabi M, Alamir B. Liquid Chromatography/Tandem Mass Spectrometry (LC-MS/MS) determination of Chlorpromazine, Haloperidol, Levomepromazine, Olanzapine, Risperidone, and Sulpiride in Human Plasma. International Journal of Analytical Chemistry. 2018;2018:5807218. DOI: 10.1155/2018/5807218.
[8] Mitrowska K, Posyniak A, Żmudzki J. Fast way of determining tranquilizers and a beta-blocker in porcine and bovine kidney using liquid chromatography with tandem mass spectrometry. Analytica Chimica Acta. 2009;637(1-2):185-192. DOI: 10.1016/j.aca.2008.10.030.
[9] Dai J, Lin H, Pan Y, et al. The quantification of chlorpromazine and its metabolites in food derived from animals by the use of QuEChERS-based extraction with EMR-Lipid cleanup and UHPLC-Q-Orbitrap MS analysis. Food Chemistry. 2023;403:134298. https://doi.org/10.1016/j.foodchem.2022.134298.
[10] Trautwein C, Kümmerer K. The environmental degradation of the tricyclic antipsychotic drug chlorpromazine and its major aquatic biotic and abiotic transformation products identified by LC-MSn and their impact on environmental bacteria. Journal of Chromatography B. 2012;889-90:24-38. DOI: 10.1016/j.jchromb.2012.01.022.
[11] Yamini Y, Faraji M. Extraction and determination of trace amounts of chlorpromazine in biological fluids using magnetic solid phase extraction followed by HPLC. Journal of Pharmaceutical Analysis. 2014;4(4):279–285. DOI: 10.1016/j.jpha.2014.03.003.
[12] Gameiro C, Gonçalves J, Soares S, et al. Evaluation of Antipsychotic Drugs’ Stability in Oral Fluid Samples. Molecules. 2023;28(5):2030. DOI: 10.3390/molecules28052030.
[13] Qi L, Duan LM, Sun XH, Zhang J, Zhang ZQ. Simultaneous determination of three banned psychiatric drugs in pig feed and tissue using solid-phase reactor on-line oxidizing and HPLC-fluorescence detection. Biomedical Chromatography. 2015;29(10):1535–1540. DOI: 10.1002/bmc.3455.
[14] Nasr MS, Al-Rufaie MMM. UV–Visible Spectrophotometric Determination of Chlorpromazine Hydrochloride from Pharmaceuticals Using Platinum (IV) Chloride. Acta Chemica Iasi. 2023;31(1):1–16. DOI: 10.47743/achi-2023-1-0001.
[15] Hammood MK, Jeber JN, Khalaf MA, Abdul hadi kharaba H. Fast colorimetric detection of chlorpromazine HCl antipsychotic by in-situ synthesis of gold nanoparticles. RSC Advances. 2024;14:2327-2339. https://doi.org/10.1039/D3RA05516G.
[16] Hassan RF, Jeber JN, Abd-Alrazack HF, Hammood MK, Abd MM. A sensitive method to determine chlorpromazine in pharmaceutical formulations and biological fluids with the help of solid phase extraction and HPLC-UV and spectrophotometric analysis. RSC Advances. 2025;15:11478-11490. DOI: 10.1039/D5RA01298H.
[17] Huang Y, Chen Z. Chemiluminescence of chlorpromazine hydrochloride based on cerium(IV) oxidation sensitized by rhodamine 6G. Talanta. 2002;57(5):953–959. DOI: 10.1016/S0039-9140(02)00142-X.
[18] Shi W, Yang Y, Liu X, Li J. Ion-pair complex-based solvent extraction combined with chemiluminescence determination of chlorpromazine hydrochloride with luminol in reverse micelles. Journal of Pharmaceutical and Biomedical Analysis. 2004;36(2):269–275. DOI: 10.1016/j.jpba.2004.05.003.
[19] Mokhtari A, Rezaei B. Chemiluminescence determination of chlorpromazine and fluphenazine in pharmaceuticals and human serum based on tris(1,10-phenanthroline)ruthenium(II). Analytical Methods. 2011;3:996-1001. DOI: 10.1039/C0AY00738B.
[20] Song M, Li C, Wu S, Duan N. Specific aptamer screening of chlorpromazine and construction of a new ratiometric fluorescent aptasensor using metal-organic framework. Talanta. 2023;252:123850. DOI: 10.1016/j.talanta.2022.123850.
[21] Hao X, Liu W, Zhang Y, Kang W, Niu L, Ai L. New and fast assay of chlorpromazine hydrochloride in biological specimens using SERS. Chemical Physics Letters. 2021;784:139066. DOI: 10.1016/j.cplett.2021.139066.
[22] Barveen NR, Wang TJ, Chang YH. A photochemical approach to anchor Au NPs on MXene as a prominent SERS substrate for ultrasensitive detection of chlorpromazine. Microchimica Acta. 2022;189(1):16. DOI: 10.1007/s00604-021-05118-z.
[23] Chen R, Chen Q, Wang Y, Feng Z, Xu Z, Zhou P, Huang W, Cheng H, Li L, Feng J. Ultrasensitive SERS substrate to label-free therapeutic drug monitoring of chlorpromazine hydrochloride and aminophylline in human serum. Analytical and Bioanalytical Chemistry. 2023;415:1803-1815. DOI: 10.1007/s00216-023-04621-x.
[24] Wang X, Chen C, Wang X, Waterhouse GIN, Qiao X, Xu Z. Ultrasensitive SERS sensor using aptamer-based 3D SERS tags as a means of simultaneous detection of levamisole and chlorpromazine in foods. Journal of Future Foods. 2025. DOI: 10.1016/j.jfutfo.2025.10.024.
[25] Zheng L, et al. Research Progress in Small-Molecule Detection Using Aptamer-Based SERS Techniques. Biosensors. 2025;15(1):29. DOI: 10.3390/bios15010029.
[26] Palanisamy S, Karuppiah C, Chen SM, et al. An Easy Electrochemical Synthesis of Reduced Graphene Oxide@Polydopamine Composites: A New Electrochemical Sensing Interface to Amperometrically Detect Chlorpromazine. Scientific Reports. 2016;6:33599. DOI: 10.1038/srep33599.
[27] Palakollu VN, Karpoormath R, Wang L, Tang JN, Liu C. A Versatile and Ultrasensitive Electrochemical Sensing Platform for Detection of Chlorpromazine Based on Nitrogen-Doped Carbon Dots/Cuprous Oxide Composite. Nanomaterials. 2020;10(8):1513. DOI: 10.3390/nano10081513.
[28] Han Q, Zhang T, Wang M, Yan F, Liu J. Disposable Electrochemical Sensors for Highly Sensitive Detection of Chlorpromazine in Human Whole Blood Based on the Silica Nanochannel Array Modified Screen-Printed Carbon Electrode. Molecules. 2022;27(23):8200. DOI: 10.3390/molecules27238200.
[29] Ma L, Pei WY, Yang J, Ma JF. Efficient Electrochemical Sensing of Chlorpromazine with a Composite of Multiwalled Carbon Nanotubes and a Thiacalix[4]arene-Based Metal-Organic Framework. Langmuir. 2024;40(33):17656–17666. DOI: 10.1021/acs.langmuir.4c02003.
[30] Tajik S, Garkani-Nejad F, Beitollahi H. Synthesis of La3 + / Co3O4 Nanoflowers as a sensitive chlorpromazine detection. Russian Journal of Electrochemistry. 2019;55:255-263. https://doi.org/10.1134/S1023193519030108.
[31] Kesavan G, Gopi PK, Chen SM, Vinothkumar V. Iron vanadate nanoparticles based on boron nitride nanocomposites as an electrochemical sensing material of antipsychotic drug chlorpromazine. Journal of Electroanalytical Chemistry. 2021;882:114982. DOI: 10.1016/j.jelechem.2021.114982.
[32] Zeng S, Zhu P, Liu D, Hu Y, Huang Q, Huang H. An electrochemical sensor that is highly sensitive to CoWO4/multi-walled carbon nanotubes in the determination of chlorpromazine hydrochloride selectively. The Analyst. 2025;150:81-86. DOI: 10.1039/D4AN01298D.
[33] Zinatloo-Ajabshir, A Pardakhty, H Mahmoudi-Moghaddam, H Akbari Javar. Green synthesis of a porous binary oxide nanocomposite using amino acids as an assistant in sensitive electrochemical detection of chlorpromazine. Scientific Reports. 2025;15:35158. DOI: 10.1038/s41598-025-19185-2.
[34] Motaharian A, Hosseini MRM, Naseri K. Estimation of psychoactive agent chlorpromazine through screen printed carbon electrodes coated with a new type of MIP-MWCNTs nano-composite synthesized via suspension polymerization. Sens. and Actuators B: Chemical. 2019;288:356-362. DOI: 10.1016/j.snb.2019.03.007.
[35] Chen J, Liu H, Wang C, Fan K, Li L, Zhang Y, Fang L, Yin Z, Lü Z. Electrochemical sensor of chlorpromazine with a molecularly imprinted interface made by a gold-copper bimetallic synergetic system on acupuncture needle electrode. Analyst. 2023;148:2214-2224. DOI: 10.1039/D3AN00373F.
[36] Lu Z, Wei K, Ma H, et al. On-off ratio signal amplified electrochemical sensor based on nanoarchitecture of molecularly imprinted polymer on-off ratiometric signal amplified electrochemical sensor chlorpromazine using Ni-MOF/Fe-MOF-5 hybrid Au nanoparticles. Separation and Purification Technology. 2023;327:124858. DOI: 10.1016/j.seppur.2023.124858.
[37] Zhao H, Liu S, Kong X, Zou R, Zhou D. Electropolymerized molecularly imprinted electrochemical sensor to detect an antipsychotic drug chlorpromazine sensitively and selectively. International Journal of Electrochemical Science. 2025;20:101076. https://doi.org/10.1016/j.ijoes.2025.101076.
[38] Liu W, Li WH, Yin WW, et al. Preparation of a monoclonal antibody and development of an indirect competitive ELISA for the detection of chlorpromazine residue in chicken and swine liver. Journal of the Science of Food and Agriculture. 2010;90(11):1789–1795. DOI: 10.1002/jsfa.4014.
[39] Shen YD, Xiao B, Xu ZL, Le HT, Wang H, Yang JY, Sun YM. Synthesis of haptens and creation of an indirect competitive enzyme-linked immunosorbent assay to detect chlorpromazine in pork, chicken and swine liver. Analytical Methods. 2011;3:2797-2803. DOI: 10.1039/C1AY05480E.
[40] Wang J, Wang Y, Pan Y, Chen D, Liu Z, Feng L, Peng D, Yuan Z. A generic monoclonal antibody was prepared and an indirect competitive ELISA with high sensitivity was developed to detect phenothiazines in animal feed. Food Chemistry. 2017;221:1004-1013. DOI: 10.1016/j.foodchem.2016.11.062.
[41] Wang W, Wang J, Wang M and Shen J. Rapid Determination of Chlorpromazine Residues in Pork with Nanosphere-Based Time-Resolved Fluorescence Immunoassay Analyzer. International Journal of Analytical Chemistry. 2021;2021:6633016. DOI: 10.1155/2021/6633016.
[42] Yeung PKF, Hubbard JW, Korchinski ED, Midha KK. Radioimmunoassay for the N-Oxide Metabolite of Chlorpromazine in Human Plasma and Its Application to a Pharmacokinetic Study in Healthy Humans. Journal of Pharmaceutical Sciences. 1987; 76(10): 803–808. DOI: 10.1002/jps.2600761011.
[43] Singh R, Rawat M, et al. A Review on Recent Trends and Future Developments in Electrochemical Sensing. ACS Omega. 2024;9(7):7336–7356. DOI: 10.1021/acsomega.3c08060.
[44] Jesky RG, Lo RHP, Siu R, et al. Designing the Future of Biosensing: Advances in Aptamer Discovery, Computational Modeling, and Diagnostic Applications. Biosensors. 2025; 15(10): 637. DOI: 10.3390/bios15100637.
Downloads
Published
Issue
Section
License
Copyright (c) 2026 World Scientific Research Journal
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
