## 3 Microextraction by Packed Sorbent
In a similar vein, [PERSON] and his research group designed and optimized two analytical methodologies for the determination of biologically active polyamines and related compounds in urine [37] and saliva samples [36]. The analytes were derivatized in situ with ethyl chloroformate using both methods prior to their isolation from the matrix using microextraction by packed sorbent and their GC-MS detection. The derivatization step was deemed to be imperative due to the high polarity and poor volatility of polyamine molecules. In the method applied to saliva samples [37], it is notable that the MEPS cartridge is reusable for up to 110 extraction cycles under optimal conditions, with impressive recovery performances for all screened analytes ranging from 89% to 109%. In the method applied to urine [38], it is significant to highlight the method's reliability, expressed as %RSD, which was assessed in terms of repeatability and reproducibility. In all cases, the %RSD values did not exceed 15%, which was considered highly satisfactory as they reflect variations across all procedures, including derivatization, extraction, and separation. In addition, LODs and LLOQs were evaluated and found to be in the low range of \(\upmu\)g/L in both methods. All of these mentioned features render each of the two methods appropriate for monitoring the studied polyamines in healthy individuals and cancer-diagnosed patients, given that bioactive polyamines have been classified as viable cancer biomarkers [60]. [PERSON] et al. also worked on the determination of polycyclic aromatic hydrocarbons (PAHs) in human urine by using a fully automated microextraction using a packed sorbent coupled to GC-MS analytical instrumentation [38]. The method involved the easy pretreatment procedures of urine samples, requiring a simple hydrolysis step and no derivatization prior to analysis. The hydrolysis step was included to convert PAHs into OH-PAHs, as the latter are considered reliable biomarkers for assessing PAH exposure levels and are more harmful to human health than their parent compounds. The automation of the method necessitated minimal sample manipulation, thus reducing errors associated with sample preparation and saving time, compared to the more sensitive LC-MS/MS previously reported methods that involve a manual sample pretreatment [61; 62; 63]. Moreover, the developed method provides the advantage of shorter durations for both the extraction process and chromatographic separation, totaling 17.5 min, compared to a previously published method [64]. The automated MEPS procedure streamlines cartridge washing, sorbent reconditioning, and subsequent sample loading during the preceding chromatographic separation run, enabling high sample throughput of up to three samples per hour. The proposed methodology was applied to urine samples from both smokers and non-smokers, and the results aligned with those of the previously described methods. Moving forward, [PERSON] et al. developed a sensitive and automatic method for the determination of unmetabolized PAHs in saliva before their biotransformation in the body, based on MEPS and GC-MS analyses [39]. The hydrolysis step could be omitted, and saliva samples were easily collected and handled during the pretreatment procedure. The main advantages highlighted by the authors include the method's full automation, where the entire analytical process (extraction, separation, and detection) occurs online, minimizing associated errors. Additionally, the MEPS workflow is notably short, requiring only 21 min per sample. Additionally, the use of more common analytical instrumentation, such as a single quadrupole mass spectrometer, makes the developed method more accessible compared to other reported methods [65; 66] that employ advanced analytical equipment, thus making it suitable for most laboratories.