Highly Sensitive and Selective Detection of the Antidepressant Amitriptyline Using a Functionalised Graphene‐Based Sensor

Abstract

The accurate measurement of drug concentration in patient samples is vital and is often conducted using point of care devices for therapeutic drug monitoring and other clinical activities. Two dimensional (2D) nanomaterials provide an opportunity to develop miniaturized, affordable and accurate drug sensors, with the promise of developing point of care tests, which are more convenient compared to current techniques that often require advanced instrumentation and laboratory tests. Here we present a reduced graphene oxidebased electrochemical sensor that permits precise measurements of amitriptyline, a well-known anti-depressant. The sensor uses functionalised graphene where amitriptyline selective receptors directly attached to the carbon atoms on the surface of the graphene through diels-alder reaction. The simplicity of the functionalisation procedure along with a tunable receptor used in this study implies that the same method can be used for developing similar selective sensors, simply by changing the small functional groups attached to the receptor molecule. The electrochemical characteristics of the functionalised graphene were studied with cyclic voltammetry, where the sensor demonstrated excellent selectivity, responding only to amitriptyline when tested against closely related tricyclic antidepressants and a range of other psychoactive drugs. The sensor displayed a wider linear range from 1 ng/mL to 80 μg/mL, which covers the concentration range for amitriptyline studied in therapeutic, pharmaceutical, and forensic investigations. The limit of detection of the developed sensor was 1 ng/ml which competes with the detection limit of gas chromatography -mass spectrometry investigated in this study.

Rapid Detection of Amitriptyline in Dried Blood and Dried Saliva Samples with Surface-Enhanced Raman Spectroscopy

“…As can be seen in Table 4 , while using DBS to measure AMT by chromatography techniques has previously been investigated [ 3 , 4 , 98 , 99 ], utilizing DSS to analyze AMT concentrations has not been reported to date. Electrochemical detection techniques can offer significantly faster response [ 2 , 100 , 101 , 102 ] compared to any other reported chromatography techniques. Despite the rapid nature of these techniques, none of the electrochemical sensors have previously been used to analyze dried biological samples.…”

“…Amitriptyline (AMT) is a common and widely used tricyclic antidepressant (TCA) for patients with major depressive disorder [ 1 , 2 ]. Similar to other TCAs, AMT displays large individual differences in clearance, and the therapeutic window of AMT is relatively small (150 ppb–300 ppb) [ 3 , 4 , 5 ]; thus, therapeutic drug monitoring (TDM) is necessary.…”

“…Among all TCAs, only amitriptyline is linked to brain death by depressing brain stem functions [ 8 ], in addition to causing sudden death by cardiac arrest [ 9 , 10 ]. Due to its hazardous nature, AMT detection is important in medical investigation, forensic pathology, and toxicology [ 2 , 11 , 12 ]. Many suicidal death cases were found to be related to the toxic effects of AMT [ 13 ].…”

Core-Labeled Reverse Micelle-Based Supramolecular Solvents for Assisted Quick and Sensitive Determination of Amitriptyline in Wastewater

“…The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.langmuir.3c03691. Chemical scheme for the receptor (ANS-2) synthesis and its crystal data; 1 H, 13 C NMR, and mass spectrometry data; picture of the biphasic system; UV−visible absorption and IR spectrum data of constituents and assembly; competitive binding, interference, and time track studies for amitriptyline sensing; chemical structures of fluorescent dyes and drug analytes used; and literature comparison (PDF)…”

“…High-resolution mass spectra (HRMS) were acquired by using a Xevo G2-XS QTof (Waters) mass spectrometer. Nuclear magnetic resonance (NMR) spectroscopy was conducted using a JEOL NMR Model JNMECS400 instrument for 1 H (400 MHz) and 13 C (100 MHz) NMR analysis. Spectra were analyzed using Mestrelab's MestreNova (v14.2).…”