## 2 Results and Discussion
### Quantitative Results (Extraction Efficacy)  
With three out of four types of coatings, the desorption solvent labelled as DS3a and composed of methanol/water/formic acid (80/19.9/0.1, \(v/v\)) yielded the best efficacy, except with the 5 \(\upmu\)m particles, which also performed worst in this evaluation, where DS1b containing isopropanol/water/ammonium hydroxide (80/19.9/0.1, \(v/v\)) was the most effective. Methanol used as a solvent has been reported to increase steric repulsion of bulky solutes better than acetonitrile [31; 32] which may explain the more effective desorption observed with this type of solvent. Steric repulsion is also determined by the density of the ligands bonded with the particle [31]; therefore, the \"more crowded\" 5 \(\upmu\)m particles may have prevented bulky solutes from being intercalated between hydrocarbon chains during the extraction and thus excluded this mechanism from influencing desorption efficacy. As mentioned before, the poorest extraction efficacy was achieved with coatings prepared with the 5 \(\upmu\)m particles. With desorption to the best performing desorption solvent type (DS1b), the extraction efficacy exceeded the median recorded for the entire dataset only in 12 out of 30 analytes (40%), and only a single analyte (methadone) extraction yield was in an upper quarter of the results. With no analyte, the best extraction efficacy was achieved with this type of coating. With the three remaining coatings, the 10 \(\upmu\)m particles yield extraction efficacies above the median for 28 out of 30 analytes (hydrocodone and oxycodone were the exceptions), within the 3 rd quartile for 18 analytes (60%); however, the best extraction efficacy was not recorded with this type of coating after desorption to the most effective desorption solvent (DS3a). The largest tested particles (45 \(\upmu\)m) performed much better, and extraction efficacy exceeding the median value was recorded for every single analyte after desorption to DS3a. Additionally, 28 results in the 3 rd quartile were recorded, as well as the largest extraction efficacy of the eight analytes. With Phenomenex(r) Synergi(tm) Hydro-RP, which are the only particles end-capped with polar functional groups, results above the median were achieved for all analytes after desorption to DS3a. One less result in the 3 rd quartile was recorded than for the 45 \(\upmu\)m particles (27 out of 30); however, concurrently, the largest extraction efficacy was recorded for more than double the number of analytes (18 out of 30, or 60%). Figure 1 shows the number of results above the median (upper half), in the 3 rd quartile (upper quarter) and the number of best results for the most effective coating-desorption solvent combinations for each coating type. The results of statistical analysis for every tested coating-desorption solvent combination are shown in the Supplementary Materials Table S2. With regard to the top extraction yields for a given analyte, most results (18 = 60% of all) were recorded for the 10 \(\upmu\)m particles with polar end-capping groups (all cases after desorption to DS3a) and for the 10 \(\upmu\)m particles with TMS end-capping in 2 cases (1 with DS3n and 1 with DS3b). For the 45 \(\upmu\)m particles, 10 cases were recorded (8 after desorption to DS3a, 1 with DS1b, and 1 with DS2a). No such results were achieved with the 5 \(\upmu\)m particles. The optimal extraction efficacies and optimal conditions for every tested analyte are shown in Table 1, and the comprehensive results with all extraction yields and corresponding relative standard deviations for every analyte are shown in Table S3 in the Supplementary Materials. Median extraction efficacy, extraction efficacy determining the 3 rd quartile, as well as top extraction efficacy for given substance are also provided in Table S3 in Supplementary Materials for easier interpretation of the results.