## 3 Microextraction by Packed Sorbent
Within this context, in the second study, lower LLOQs (0.05 ng/mg) and LODs (0.01 ng/mg and 0.05 ng/mg for ketamine and norketamine, respectively) were comfortably achieved, despite the lower obtained recoveries (<50%) [33]. Hence, the second GC-MS/MS method seems to be more sensitive than the first one. Another category of analytes, amphetamine-type stimulants, attracted the interest of [PERSON] et al. [31]. Amphetamines are chemically synthesized psychoactive compounds, like several neurotransmitters, that are widely consumed by drug abusers. Consequently, their determination in biological fluids remains a crucial issue in toxicological analysis [48]. [PERSON] and her colleagues developed and fully validated a MEPS-GC-MS method for amphetamine determination in urine samples [31]. By using only 200 \(\mu\)L of a sample, satisfactory recoveries and adequate LODs and LOQs were observed, with a larger number of compounds being analyzed compared to other reported methods [49; 50; 51; 52]. The overall bioanalytical protocol was revealed to be simple, rapid (extraction process < 3 min), sensitive, selective, and accurate. In the same context, cannabis and related products are considered some of the most available (or diffused) and abused illicit drugs worldwide [53]. The determination of some cannabinoids in biological samples can be challenging for various reasons. In particular, in addition to the matrix complexity of body fluids, cannabinoids are extensively metabolized and may disappear quickly from the bloodstream, are highly lipophilic, tend to accumulate in fatty tissues, and remain in low concentrations in aqueous biological fluids. Furthermore, they have a short detection window (for a few hours and up to a day) and individual variability (body fat percentage, frequency of use, etc.) that affects cannabinoid concentration, making it harder to standardize detection thresholds [54]. Despite the aforementioned limitations, several research groups have developed methods for their detection. [PERSON] et al. established two bioanalytical protocols for the trace-level determination of cannabinoids and their main metabolites in urine [34] and human plasma samples [35] using MEPS prior to GC-MS and GC-MS/MS, respectively. In both methods, a small sample volume of 250 \(\mu\)L was used. In the first study [34], the method was considered suitable for cannabinoid determination, noting that, for all cannabinoids, lower LLOQs were achieved (1-10 ng/mL) than the recommended cut-off concentrations (50 ng/mL) for laboratory screen tests. In the second study [36], although the sample needed to be diluted 20 times, the method's sensitivity was not affected, and very low LLOQ values for all analytes were obtained (0.1 ng/mL), taking into consideration the limitations of the cannabinoid's metabolic profile. The sensitivity and extraction recoveries of the method were also enhanced by employing an increased number of 26 sample strokes, in order to ensure sufficient sorption of the analytes on the sorbent bed. Finally, [PERSON]'s research group designed and validated a method for the quantification of six organophosphorus pesticides in whole blood samples by MEPS and GC-MS/MS analysis [45]. The method was found to be selective, as no signals deriving from other compounds that could be present in authentic samples were detected at the corresponding retention times and transitions of the studied compounds. The recoveries obtained were comparable to those of other methods that used larger sample volumes [45; 55; 56; 57]. In contrast, the described method required only 150 \(\mu\)L of the sample for MEPS. The authors pointed out that a higher number of sample loading cycles by using an automated MEPS system could yield better responses and even higher recoveries. Regarding the LLOQs, although higher values were achieved compared to other published studies [58; 59], the method was deemed appropriate for quantitative analysis in cases of acute poisoning where elevated concentrations of the studied compounds are typically observed.