Abstract Collection From the Second Conference of Therapeutic Drug Monitoring – TDM 2025

Cardiac arrhythmia affects approximately 12.6% of people over the age of 65. Ventricular arrhythmias are considered as responsible for 75%–80% of sudden cardiac deaths. Therapeutic drug monitoring in antiarrhythmic drugs (AAD) is essential for patient management because of narrow therapeutic range, association with several serious adverse drug reactions, and long multiphasic elimination or formation of active metabolites with the action distinct from the parent drug. Developed assay named “CardioCarePack” is based on the use of capillary blood collected at home by a patient with volumetric absorptive microsampling (VAMS), quantitative analysis of selected drugs and their metabolites, and a telemedical system that integrates all data between a doctor, patient, and laboratory to support therapy process. The sample preparation procedures for venous and capillary blood collected with 20 μL MITRA^® microsampling device, sample transport conditions, and LC–MS/MS method on SCIEX QTRAP spectrometers were developed and validated for 17 compounds. Quantitative analysis covered therapeutic range of the tested compounds: 0.25–25 ng/mL (digoxin and nebivolol) 2.5–250 ng/mL (metoprolol, bisoprolol, propafenone, carvedilol, perindopril, ramipril, spironolactone, and zofenopril), and 25–2500 ng/mL (sotalol, desethylamiodarone, eplerenone, amiodarone, and 5-hydroxypropafenone). A total of 324 patients had been monitored for 2 years during regular pharmacological therapy. Patients were divided into four groups with the main AAD drug: amiodaron, propafenone, sotalol, and digoxin, where additional AAD could also be administered. Every half a year during a visit in medical facility, venous and capillary blood (VAMS) were collected. Between the visits, patients were collecting samples with a MITRA^® device themselves at home. Recommended transport conditions for AAD MITRA^® samples in string polyethylene bags are 20°C, desiccator, and up to 5 days. Interlaboratory study showed excellent reproducibility of the assay (80%–120%, p < 0.05). On the basis of samples collected during visits in medical facility, a correlation between drugs concentration in venous blood (serum) and capillary blood (MITRA^®) (S/M) was calculated. S/M ratio was close to 1 (e.g. sotalol – 0.95, %CV – 5.12%, nebivolol – 1.03, %CV – 3.17%) or moderately to more than twofold different (e.g. digoxin – 0.69, %CV – 1.46%, ramipril – 1.18, %CV – 11.1, perindopril – 1.86, %CV – 4.73%, amiodarone – 2.17, %CV – 10.78). The correlation factors are statistically significant (p < 0.05) and can be used for accurate concentration estimation in serum. During the clinical study, concentration of the compounds was maintained within the therapeutic range and never exceeded the upper limit of the norm. This resulted in only 11 patients with implantable cardioverter-defibrillator (ICD) or cardiac resynchronization therapy device (CRT-D) interventions and only 31 patients with arrythmia episodes (3.6% and 10.1% of the tested group, respectively). CardioCarePack helps in doctor’s supervision over the patient’s condition on the basis of data collected within the developed software (history, doses, therapeutic index flagging, cardiograms, and other diagnostic results) and fits in with modern trends of home-based sample collection and personalized medicine.

cardiac arrhythmia, TDM, VAMS, LC–MS/MS, personalized medicine.

The project was co-financed by The National Centre for Research and Development and European Regional Development Fund (Grant no: POIR.01.01.01-00-1196/19).

Therapeutic drug monitoring (TDM) and biobanking are relatively new areas that are gaining attention and gradually becoming more established in practice. Their implementation is essential to optimize therapeutic drug levels in order to achieve maximum efficiency while minimising the risk of adverse effects. The success depends on proper implementation in all analytical phases – from the pre-analytical, analytical, and post-analytical phases to the medical and pharmacological interpretation of the results. Biobanks play a key role in providing researchers with access to high-quality biological samples and data, thereby supporting the development of new diagnostics, biomarkers, and pharmaceutical treatments. The collection, processing, and archiving of biological material require well-defined handling procedures, including collection, transport, storage, and quality control of samples. Proper documentation and preservation of data at each stage enable their later use in clinical practice, medical, or pharmacological research. As these fields continue to evolve, their integration into routine practice will play a crucial role in advancing precision medicine and improving patient outcomes. This presentation will focus on the importance of TDM and biobanking, identify key challenges, and suggest strategies to improve sample quality. High-quality samples are crucial for accurate interpretation of results and effective therapeutic decision-making.

biobanking, pre-analytical phase, analytical phase, post-analytical phase, TDM.

Ambient mass spectrometry has significantly enhanced the detailed insight into the molecular composition of complex biological surfaces under native conditions, requiring minimal sample preparation (Venter et al., 2008). In the last decade, the laser ablation/desorption followed by the post-ionization of the desorbed neutral aerosol by an ionization source, particularly electrospray ionization, atmospheric pressure chemical ionization, and atmospheric pressure photoionization, has been strongly favored. Advancements in laser-based designs, including UV and deep UV lasers, enable non-destructive, low-fragmentation analysis of various solid samples and dried spots/layers while significantly improving spatial resolution for mass spectrometry imaging (MSI) to just a few micrometers (Papoušková et al., 2025). The presented work introduces a novel, fully automated remote deep-ultraviolet laser ablation coupled with electrospray ionization−atmospheric pressure chemical ionization (rDUVLAESCI) source, which can be easily used for either spot analysis or MSI of a wide range of polarity and molecular weights of organic molecules. The rDUVLAESCI benefits from the coupling of a 193-nm Analyte G2 laser ablation unit (Photon Machines) with a hybrid Q-TOF mass spectrometer Synapt G2S (Waters), enabling the simultaneous acquisition of complementary ESI and APCI mass spectra in a single analytical run. The rDUVLAESCI MS has been utilized in the analysis of dried spots of polar molecules (e.g. caffeine, new psychoactive substances (NPSs), and PEG600) and nonpolar molecules (e.g. squalene, fluorene, anthracene, and wax esters) with excellent limits of detection down to tenths of nmol/mL and attomoles per ablated/desorbed pixel, respectively. The applicability of rDUVLAESCI in molecular MSI was demonstrated on visualization of the NPSs on the latent fingerprints with a variable lateral resolution in the 25–110 μm range. The rDUVLAESCI-MSI provided a detailed insight into the spatial distribution of exogenous naphyrone, butylone, cathinone, flephedrone, tetrahydrocannabinol (THC), hexahydrocannabinol (HHC) as well as human sebum-derived molecules, including free fatty acids, squalene, cholesterol, wax esters, diacylglycerols, and triacylglycerols. The reconstructed 2D maps of sebum constituents were successfully used for personal identification. The unambiguous identification of individuals was achieved even in the case of partially overlapped fingerprints (Papoušková et al., 2025). Furthermore, the rDUVLAESCI-MSI holds great potential for quantitative analysis and imaging of molecules directly in thin tissue sections (12–30 μm thick) due to its ability to optimize laser fluence for complete sample ablation and desorption. The mouse brain and skin melanoma samples were recently subjected to the rDUVLAESCI-MS/MSI. In the brain tissue, the main molecules detected were cholesterol and its derivatives (dehydrocholesterol, oxocholesterol, and desmosterol), free fatty acids (palmitic acid and linolenic acid), sphingosine, diacylglycerols (mainly dipalmitoyl glycerol), phospholipids, and C18 ceramide and adenine. In cancerous tissue, adenine was one of the key analytes, while the free fatty acids were most abundant. Identification was performed based on accurate mass measurements using cholesterol present in the tissue used as the lock mass. To conclude, rDUVLAESCI-MS/MSI opens a new window for the detailed studies of the plethora of molecules with significantly different polarity and molecular weight, which can be adopted in advanced disease diagnosis, environmental protection, and other research fields.

mass spectrometry, imaging, new psychoactive substances, fingerprints, laser ablation.