Multidimensional Liquid Chromatography Employing a Graphene Oxide Capillary Column as the First Dimension: Determination of Antidepressant and Antiepileptic Drugs in Urine

Abstract

Human mental disorders can be currently classified as one of the most relevant health topics. Including in this are depression and anxiety, which can affect us at any stage of life, causing economic and social problems. The treatments involve cognitive psychotherapy, and mainly the oral intake of pharmaceutical antidepressants. Therefore, the development of analytical methods for monitoring the levels of these drugs in biological fluids is critical. Considering the current demand for sensitive and automated analytical methods, the coupling between liquid chromatography and mass spectrometry, combined with suitable sample preparation, becomes a useful way to improve the analytical results even more. Herein we present an automated multidimensional method based on high-performance liquid chromatography-tandem mass spectrometry using a lab-made, graphene-based capillary extraction column connected to a C8 analytical column to determined five pharmaceutical drugs in urine. A method enhancement was performed by considering the chromatographic separation and the variables of the loading phase, loading time, loading flow, and injection volume. Under optimized conditions, the study reports good linearity with R2 > 0.98, and limits of detection in the range of 0.5–20 µg L−1. Afterward, the method was applied to the direct analysis of ten untreated urine samples, reporting traces of citalopram in one of them. The results suggest that the proposed approach could be a promising alternative that provides direct and fully automated analysis of pharmaceutical drugs in complex biological matrices.

Recent Advances in Analytical Techniques for Antidepressants Determination in Complex Biological Matrices: A Review

“…As mentioned above, biospecimens where antidepressants are usually detected include urine, 24,51,53-55,61,64,65 whole blood, 11,17,22,23,29,31,35,36,39,41,57,58 dried blood spots, 11,32 plasma, 23,26,28,48,48,60,63 serum, 23,40,46,50,63,65 hair, 44,51 OF, 30,62,67 pericardial fluid, 14 bone marrow, 33,52,66 bones, 21,25,34,47,59 brain tissue, 36 intraosseous fluid, 26 meconium, 56 and VH 12,13 with each matrix requiring specific treatment depending on the type of antidepressant under investigation.…”

“…The majority of these techniques rely on LC approaches, utilizing MS/MS detection modes, 60,62,63 TOF/ MS, 33,52 and U(H)PLC with MS/MS. 29,46,47,51,61 Additionally, several studies employed GC coupled to MS detection [12][13][14]20,22,[24][25][26]34,62 or tandem MS detection modes. [15][16][17]19 Most frequently, these methods have shown low detection limits, selectivity, sensitivity, and acceptable results, enabling precise quantification of ADs.…”

“…Maciel et al (2020) 61 presented an automated multidimensional technique based on LC-MS/MS utilizing a lab-made, graphene-based capillary extraction column coupled to a C8 analytical column to determine four ADs, such as desipramine, clomipramine, citalopram, and carbamazepine, and 1 anticonvulsant AC, sertraline, in urine. The study reports good linearity (R2 > .98), and LODs were in the range of .5 to 20 μg/L.…”

Modern automated microextraction procedures for bioanalytical, environmental, and food analyses

“…Later in 2020, Maciel et al employed Si@GO particles for column-switching analysis of antidepressant and antiepileptic drugs in urine. The use of the graphene-based extractive phase showed a good affinity with molecules containing aromatic rings like the pharmaceutical drugs analyzed, where π-π interactions resulted in selective extraction [107]. In 2021, with the use of three different columns, Pot et al [108] built mD-LC-MS as a bottom-up approach for the analysis of formulated monoclonal antibodies and antibody-derived therapeutics.…”

Applicability and Limitations of a Capillary-LC Column-Switching System Using Hybrid Graphene-Based Stationary Phases

“…For example, extraction columns (also known as pre-concentration columns) packed with SiGO-C18ec particles have been applied with success in studies of pesticides in sugarcane spirits [ 30 ], mycotoxin separation in beverages [ 31 ], and xanthines in coffee beverages [ 32 ]. Examples of their application in a column-switching setup containing SiGO particles in the extraction column are the determination of β-lactams from environmental water samples [ 33 ], pesticides in sugarcane spirits [ 30 ], and resolution of antidepressant and antiepileptic drugs in urine [ 34 ].…”