Table 2.
Liquid-phase sample preparation techniques for tyrosine kinase inhibitors (TKIs) in different biological material.
| Biological material | Analytes | Pretreatment method | Extraction process | Sample size | Recovery | Monitoring metabolites | Samples from patients | Potential for clinical application | Refs. |
|---|---|---|---|---|---|---|---|---|---|
| Fresh human urine and plasma | 2 TKIs | SA-SHS-LPME | Transfer 10 mL of sample solution containing 50 μg/L of imatinib and N-desmethyl imatinib to a 15 mL centrifuge tube, add 600 μL of the P-TEA-C and 1.5 g of NaCl to each tube and centrifuge (2 min), add 2.0 ml 10 M NaOH solution and centrifuge (4,000 r/min, 5 min), and collect the TEA phase which floated on the surface and dry it (evaporating under nitrogen) | 4 mL | 97.0%–102% | No | No | No | [15] |
| Human plasma | 2 TKIs | LLE | Add 0.5 mL of ethyl acetate to the samples, vortex for 1 min, stand for 1 min (room temperature) and centrifuge (12,000 g, 10 min, 4 °C), and dry upper organic phase (vacuum volatilization, room temperature) | 3 mL | 89.6%–92.9% for imatinib and 87.7%–91.9% for N-demethyl-imatinib | Yes | Yes | Yes | [33] |
| Human plasma | 3 TKIs | LLE | Add 1.2 mL of ethyl acetate to each tube, vortex (5 min) and centrifuge (15,000 r/min, 10 min, 4 °C), and dry upper organic phase (evaporating using a Thermo Electron RVT4104 refrigerated vapor trap, 35 °C) | 300 μL | 53.2%–67.9% for imatinib, 63.7%–71.8% for dasaitinb, and 82.6%–103.4% for nilotinib | No | Yes | Yes | [34] |
| Human plasma | 2 TKIs | LLE | Add 100 μL of 10% ammonia solution to each tube and vortex (30 s), add 5 mL of ethyl acetate, vortex (3 min) and centrifuge (1,690 g, 10 min), and dry upper organic phase (evaporating under nitrogen, 37 °C) | 500 μL | 78.93%–96.54% | Yes | Yes | Yes | [35] |
| Artificial human serum | 2 TKIs | LLE | Add 20 μL of 1 M NaOH solution to adjust the pH, add 0.8 mL of tert-butyl methyl ether into aliquots of serum, vortex (2 min) and centrifuge (10,000 g, 5 min), collect upper organic phase and extract the aqueous part once more with 4 mL of tert-butyl methyl ether, and dry the combined upper organic phase under vacuum in an Eppendorf Vacufuge Concentrator | 0.5 mL | ≥83% | Yes | No | No | [36] |
| Human plasma | 7 TKIs | LLE | Add 50 μL of acetonitrile to the samples and vortex for 20 s, add 1 mL of ethyl acetate and tert-butyl methyl ether (1:1, V/V) to each tube, vortex (30 s) and centrifuge (10,000 g, 10 min), and dry upper organic phase (evaporating, 40 °C) | n.d. | ≥70% | No | No | Yes | [37] |
| Human plasma | 6 TKIs | LLE | Vortex samples (a few seconds), add 700 μL of ethyl acetate to each tube, vortex (30 s) and centrifuge (10,000 r/min, 5 min), and dry upper organic phase (evaporating under nitrogen flow) | 150 μL | n.d. | Yes | Yes | Yes | [38] |
| Human plasma | 6 TKIs | LLE | Add 500 μL ethyl acetate:tert-butyl methyl ether (1:1, V/V) to each tube, vortex (1 min) and centrifuge (10,000 g, 5 min, 4 °C), and dry upper organic phase (evaporating under a stream of nitrogen, 40 °C) | 20 μL | 88.3%–103.6% | No | Yes | Yes | [39] |
| Rat plasma | 1 TKIs | SALLE | Dissolve 350 mg of NaCl in 1 mL of sunitinib-spiked plasma followed by the addition of 500 μL of acetonitrile, vortex (1 min) for phase separation, and suck out the upper layer (200 μL) | 1 mL | 87.4%–123.32% | No | No | No | [40] |
| Human plasma | 12 TKIs | SALLE | Add 200 μL of acetonitrile and then add 100 μL of 5 M ammonium acetate solution. Next, vortex (3 min) and centrifuge (12,000 g, 10 min, 4 °C) | 100 μL | 83.19%–112.04% | No | Yes | Yes | [41] |
| Human plasma | 3 TKIs | On-line SALLE | Mix relevant volumes of plasma solution and three TKIs stock solutions in Eppendorf tube to obtain a final volume of 80 μL (1 h, room temperature) and place the Eppendorf tube in the CE plastic vials | n.d. | n.d. | No | No | Yes | [42] |
| Human plasma | 4 TKIs | SALLE | Add 3 mL of acetonitrile to 2 mL of standard solution and vortex (1 min), add 0.1 g of 2% NaCl (m/V) and vortex (1 min), and stand (3 min) | n.d. | n.d. | No | Yes | Yes | [43] |
| Human serum and cerebrospinal fluid | 4 TKIs | SC-SF-SLDME | Adjust the pH of samples to 11.0, add appropriate amount of NaCl with final concentration 10% (m/V), add 1.5 mg of MNi-CNT hybrid and immerse in an ultrasonic water bath for 30 s, insert 30 mL of 1-undecanol and stir with glass-coated magnet (600 r/min for 5 min, 300 r/min for 5 min), ice bath, collect 1-undecanol, and elute the MNi-CNT using acetonitrile | 2 mL | 84.0%–98.5% | No | No | No | [47] |
n.d.: not discovered. SA-SHS-LPME: salting-out-assisted switchable hydrophilicity solvent-based liquid-phase microextraction; P-TEA-C: protonated triethylamine carbonate; LLE: liquid-liquid extraction; SALLE: salt-out assisted LLE; CE: capillary electrophoresis; SC-SF-SLDME: stirring-controlled solidified floating solid-liquid drop microextraction; MNi-CNT: magnetic carbon nanotube-nickel hybrid.