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Solid-Phase Extraction and Clean-Up Procedures in Pharmaceutical Analysis

Pharmaceuticals and Drugs

  1. P. Campíns-Falcó,
  2. A. Sevillano-Cabeza,
  3. R. Herráez-Hernández,
  4. C. Molins-Legua,
  5. Y. Moliner-Martínez,
  6. J. Verdú-Andrés

Published Online: 17 DEC 2012

DOI: 10.1002/9780470027318.a1920.pub2

Encyclopedia of Analytical Chemistry

Encyclopedia of Analytical Chemistry

How to Cite

Campíns-Falcó, P., Sevillano-Cabeza, A., Herráez-Hernández, R., Molins-Legua, C., Moliner-Martínez, Y. and Verdú-Andrés, J. 2012. Solid-Phase Extraction and Clean-Up Procedures in Pharmaceutical Analysis . Encyclopedia of Analytical Chemistry. .

Author Information

  1. Universitat de Valencia, Valencia, Spain

Publication History

  1. Published Online: 17 DEC 2012
Table 1. Sorbents and Interaction Mechanisms in SPE
InteractionSorbentChromatographic modeAnalyte functional groupsMatrix
  1. C18, octadecyl; C8, octyl; C2, ethyl; SXC, benzenesulfonic acid; PRS, propylsulfonic acid; CBA, carboxylic acid; SAX, quaternary amine; PSA, primary/secondary amine; DEA, diethylaminopropyl.

 SI-based bonded phase   
HydrophobicC18Reversed phaseAromatic ringsAqueous
Nonpolar–nonpolarC8 Alkyl chains 
Van der Waals forcesC2   
Hydrophilic polar–polar hydrogenCNNormal phaseHydroxylsNonpolar
Bridges p–p bond2OH Amines 
Dipole–dipoleNH2 Heteroatoms (S, O, N) 
Induced dipole–dipole    
Ion-exchangeSXCIon exchangeAminesAqueous
 PRS Pyrimidines 
 PSA Sulfonic acids 
 NH2 Phosphates 
Multiple hydrophobic/ion exchangeMixed bonded SIReversed phase and Ion exchangeAcidic, neutral, and basic compoundsAqueous
 No bonded phase   
Hydrophilic/ hydrophobicSINormal phaseGenerally used to provide class separation by dividing the sample into fractions containing a similar number and type of functional groupsNonpolar
 Diatomaceous earth   
 Activated carbon   
Hydrophobic/ hydrophilicCopolymer resinsReversed phaseAromatic ringsAqueous
   Alkyl chains 
CovalentPBAReversed phaseNucleotides, nucleosidesAqueous
Table 2. Strategies for Improving Sample Clean-Up by SPE
Inadequate analyte retentionPolarChange to more nonpolar solvent
 NonpolarChange to more polar solvent
  Ionic strength ≤0.1
  Bad activation
  Ionic analyte
 Ion exchangerDilution
  Change the pH
  Decrease the ionic strength
InadequatePolarStudy the secondary mechanism
ElutionNonpolarModify the ionic strength
  Increase the nonpolar solvent
 Ion exchangerIncrease the elution volume
Poor sample clean-upPolar, nonpolar, ion exchangerIncrease the strength of the matrix washing solvent
Poor reproducibilityPolar, nonpolar, ion exchangerProtein binding
  Analyte absorption on the sorbent pH
Table 3. Representative Examples of the Use of SPE Cartridges for Sample Clean-Up in Drug Monitoring
AnalyteStudied sorbentMatrixSeparation and detection techniquesReference
Screening of amiloride, acetazolamide, hydrochlorothiazide, triamterene, chlorthalidone, furosemide, cyclothiazide, bendroflumethiazide, bumetanide, ethacrynic acid, probenecid, and spironolactoneC18, C8, C2, CH, PH and cyanoUrineHPLC with photodiode arrayCampíns-Falcó et al.40, 41
Screening of stimulants, narcotics, sedative hypnotics, antidepressants, antipsychotics, antihistamines, cardiovascular drugs, analgesics, and some derivativesBond Elut Certify (mixed-mode)Urine or serumHPLC with photodiode arrayLai et al.42
Screening of cephalexin, cefotaxime, cefazolin, cefuroxime, and cefoxitinC18, C8, C2, CH, PH, cyano cartridges, and 3 M Empore disk C18UrineHPLC with diode arrayGallo-Martinez et al.43
Screening of benzodiazepines and imidazo-pyridines, antidepressants, antipsychotics, central analgesics, anticonvulsants, antimalarials, b-blocking and b-against agents, drugs to treat cardiac diseases, alkaloids, anticoagulants, analgesics and anti-inflammatory drugs, barbiturates, and carbamatesC18Powdered hairHPLC with photodiode array and GC/MSGaillard and Pepin44
Determination of teophiline, paraxanthine, caffeine, and cefoxitinC18UrineHPLC with diode arrayCampíns-Falcó et al.45, 46
Determination of ethacrynic acidC18UrineHPLC with diode arrayCampíns-Falcó et al.47
Determination of probenecidC18UrineHPLC with diode arrayCampíns-Falcó et al.48
Determination of cefuroxime3 M Empore disk C18UrineHPLC with diode arrayGallo-Martinez et al.43
Determination of cocaine, benzoylecgonine, and cocaethyleneCopolymeric phase combining C8 and strong cation exchangeUrineHPLC with diode arrayClauwaert et al.49
Amphetamine and methamphetamine with NQS as derivatizing reagentC18, C18, C8, C2, CH, PH, and cyano cartridgesUrineHPLC with diode arrayCampíns-Falcó et al.50
    Molins-Legua et al.51
MethadoneHydrophobic and cation-exchange disk (mixed-mode)SerumHPLC with UVRudaz and Veuthey52
Determination of antimalarial drug proguanil and its metabolites, cycloguanil, and 4-chlorophenyl biguanideCN endcappedPlasma, whole blood, and urineHPLC with UVBergqvist et al.53
PhenytoinC18Human breast milk, maternal plasmaHPLC with UVShimoyama et al.54
OxycodoneC18PlasmaHPLC and electrochemicalWright et al.55, de la Torre et al.56
Tricyclic antidepressantsBond Elut TCAPlasmaCapillary GC with nitrogen–phosphorus 
Determination of ecstasy (methylenedioxymethamphetamine), methamphetamine, and methylenedioxy-ethamphetamineC8UrineGC/MSSzignan et al.57
Table 4. Methods for Determination of Drugs in Urine, which Integrate Clean-Up and Derivatization in the Same Process
AnalyteStudied sorbentDerivatizing reagentSeparation and detection techniquesReference
Amphetamine and methamphetamineC18 cartridge and precolumnNQSHPLC with diode arrayCampíns-Falcó et al.68
    Herráez-Hernández et al.69
Norephedrine, ephedrine, pseudo-ephedrine, amphetamine, 3-phenylpropylamine, and methamphetamineC18, C8, C2, CH, PH, CN cartridges, and 3 M Empore C18 disk3,5-Dinitrobenzoyl chlorideHPLC with diode arrayHerráez-Hernández et al.70
Norephedrine, ephedrine, pseudo-ephedrine amphetamine, methamphetamine, and 3-phenylpropylamineC18 cartridge and precolumn9-Fluorenylmethyl chloroformateHPLC with fluorescenceHerráez-Hernández et al.71
Amphetamine and methamphetamineC18 cartridge and precolumnDansyl chlorideHPLC with fluorescence and chemiluminescenceMolins-Legua et al.72
Putrescine, cadaverine, spermidine, and spermineC18 cartridgeDansyl chlorideHPLC with fluorescenceMolins-Legua et al.73