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Analytica Chimica Acta

Analytica Chimica Acta

IF: 5.7
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Therapeutic Drug Monitoring of Methotrexate by Disposable SPCE Biosensor for Personalized Medicine

Published:23 November 2024 DOI: 10.1016/j.aca.2024.343473
Hui Liu, Yi-Wei Liu, Meng-Meng Liu

Abstract

Background

Methotrexate (MTX) is widely used in clinical practice for the treatment of malignant tumors and autoimmune diseases. High-dose MTX has been shown to be an effective approach for treating various malignant tumors, but it is accompanied by numerous toxic side effects, necessitating therapeutic drug monitoring (TDM) for patients and timely “folinic acid rescue.” High-performance liquid chromatography and fluorescent immunoassay (FIA) are currently used to detect MTX, but these methods are limited by complex sample preparation, time consumption, and high cost. Therefore, a simple, rapid, and cost-effective MTX measurement method is required.

Results

We developed a flexible and inexpensive electrochemical sensor using a stearyl trimethyl ammonium bromide (STAB)-modified, screen-printed carbon electrode to directly detect MTX in human serum. Assay performance was validated via detection of MTX in spiked buffer. The sensor was capable of measuring MTX concentrations ranging from 0.01 to 1?μM and 1–1500?μM, with a limit of detection of 3.1?nM and a limit of quantitation of 3.5?nM. For the samples simulating combined medication, the sensor exhibited outstanding selectivity, in cross-reactivity, with the maximum response value of interferents reaching only 3.49?%. Additionally, the sensor shows reliable repeatability with a relative standard deviation of 3.8?% and remarkable stability. Recovery in human serum validated the clinical utility of the sensor in point-of-care testing conditions. The sensor's applicability to personal medicine was confirmed by detecting MTX blood concentration in patients with different diseases. The results obtained by the sensor were compared with those obtained by the FIA technique, a method commonly used in hospitals, showing a high level of consistency between both methods.

Significance

To meet the requirements of personalized medicine for MTX-patients, we developed a disposable biosensor with wide detection range from 0.01 to 1?μM and 1–1500?μM. Owing to the effective enrichment of STAB, the electrochemical response was sensitive, selective, stable, and rapid. As per the clinical test results, our sensor has shown a high level of consistency with the FIA method, indicating its potential to replace FIA as a cost-effective platform for MTX-TDM.

Substances (9)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Ascorbic Acid 50-81-7 C6H8O6 1968 suppliers $6.00-$2380.00
Sodium bicarbonate 144-55-8 CH2O3.Na 1698 suppliers $10.00-$5020.00
Folic acid 59-30-3 C19H19N7O6 1510 suppliers $5.00-$1269.63
Hexadecyl trimethyl ammonium bromide 57-09-0 C19H42BrN 974 suppliers $4.00-$19422.00
Sodium triacetoxyborohydride 56553-60-7 C6H10BNaO6 728 suppliers $10.00-$8250.00
Creatine 57-00-1 C4H9N3O2 548 suppliers $5.00-$1648.17
Acetazolamide 59-66-5 C4H6N4O3S2 430 suppliers $11.00-$600.00
Uric acid 69-93-2 C5H4N4O3 351 suppliers $8.00-$1880.00
3-Hydroxytyramine 51-61-6 C8H11NO2 200 suppliers Inquiry

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