# Solid Phase-Based Microextraction Techniques in Therapeutic Drug Monitoring
## 3 Sample Pretreatment--Solid Phase-Based Microextraction Techniques
### Microextraction by Packed Sorbent
** \\ \hline \multirow{4}{*}{Zonisamide} & \multirow{4}{*}{100 \(\mu\)L of plasma} & \multirow{4}{*}{Protein precipitation with 400 \(\mu\)L of ice-cold} & \multirow{4}{*}{} & \multirow{4}{*}{} & \\  & & & & & \\  & & & & & \\  & & & & & \\  & & & & & \\  & & & & & \\  & & & & & \\  & & & & & \\  & & & & & \\  & & & & & \\ \hline \multirow{4}{*}{Larmorigine} & \multirow{4}{*}{100 \(\mu\)L of plasma} & \multirow{4}{*}{} & Protein precipitation with 400 \(\mu\)L of ice-cold} & \multirow{4}{*}{} & \\  & & & & & \\  & & & & & \\  & & & & & \\  & & &  
\begin{table}
\begin{tabular}{c c c c c c} \hline \hline
**Analyytes** & **Sample (Amount)** & **Sample Pretreatment and Extraction Procedure** & **Analytical Technique** & **LOD, LOQ** & **Linear Range** & **Ref. ** \\ \hline  & & VANG (20 ul.) absorption for 5 s, drying for 1 h & 2.5 and 7 mg/ml. (Steintein, & 7-800 mg/ml. (Steinteintein, \\  & at room temperature and ultrasound-assisted & & Nover  
Regarding serum samples, [PERSON] and [PERSON] [19] developed a method for the identification of five immunosuppressants (cyclosporine A, everolimus, mycophenolic acid, sirolimus and tacrolimus) in 150 uL of serum, with sample preparation accomplished by MEPS using C18 sorbent and analysis by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). The method was linear over a range of 1 to 50 ng/mL for all compounds, and it was applied to post-transplant patients. More recently, [PERSON] et al. [20] established a method for the therapeutic monitoring of some antipsychotics (chlorpromazine, clozapine, olanzapine and quetiapine) in only 100 uL of plasma, with extraction by MEPS, analysis by ultra-high pressure liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS) and application to samples from schizophrenic patients. Using a restricted access carbon nanotube as a selective stationary phase for extraction, they reached a limit of quantification (LOQ) of 10 ng/mL for all compounds and concluded that the method is capable of determining these antipsychotics at sub-therapeutic levels in a reduced sample volume. [PERSON] et al. [21], using the MEPS technique with a C2 sorbent and analysis by liquid chromatography with sequential spectrophotometric and spectrofluorimetric detection, developed a methodology for monitoring eight antidepressantsants and metabolites (sertaline, norsertraline, fluoxetine, norfluoxetine, citalopram, N-desmethylcitalopram, N,N-desmethylcitalopram and vortioxetine) in 100 uL of whole blood and oral fluid. The method was validated, LOQs between 1 and 10 ng/mL were obtained, and it was applied to patients suffering from major depression and/or related disorders. Previously, [PERSON] et al. [18] validated a methodology for two antidepressants and a metabolite in plasma (500 uL), using a C18 sorbent and analysis by liquid chromatography with fluorescence detection, for which an LOQ value as low as 20 ng/mL was obtained for fluoxetine and norfluoxetine. It should be noted that the MEPS technique was used by [PERSON] et al., who developed two methods, one for the determination of catecholamines and metanephrines in urine [23] and another for the quantification of metanephrins in plasma [24], with the objective of being applied in routine clinical laboratories for the diagnosis and screening of pheochromocytoma and paraganglioma neuroendocrine tumors.