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Handbook of Drug Monitoring Methods pp 67–86Cite as

Analytical Techniques for Measuring Concentrations of Therapeutic Drugs in Biological Fluids

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Summary

Different types of assays are used in clinical laboratories for determination of concentrations of various drugs in biological fluids for therapeutic drug monitoring. Historically, concentrations of various anticonvulsants such as phenytoin, carbamazepine, phenobarbital, and primidone in serum or plasma were measured using gas chromatography (GC) or high-performance liquid chromatography. Later, these assays were replaced by immunoassays because of automation as well as need for faster turnaround time. Minimal or no specimen pretreatment is needed for analysis of various drugs in sera using immunoassays. However, immunoassays are not available for all drugs monitored in clinical laboratories, for example lamotrigine, protease inhibitors, and new generation of anticonvulsants. For analysis of these drugs, GC, HPLC, or HPLC combined with tandem mass spectrometric techniques are used.

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References

  1. Jolley ME, Stroupe SD, Schwenzer KS, Wang CJ, et al. Fluorescence Polarization immunoassay III. An automated system for therapeutic drug determination. Clin Chem 1981; 27: 1575–1579.

    PubMed  CAS  Google Scholar 

  2. Hawks RL, Chian CN, eds. Urine Testing for Drugs of Abuse. Rockville, MD: National Institute of Drug Abuse (NIDA), Department of Health and Human Services; 1986. NIDA research monograph 73.

    Google Scholar 

  3. Jeon SI, Yang X, Andrade JD. Modelingof homogeneous cloned enzyme donor immunoassay. Anal Biochem 2004; 333: 136–147.

    Article  PubMed  CAS  Google Scholar 

  4. Datta P, Dasgupta A. Anew turbidimetric digoxin immunoassay on the ADVIA 1650 analyzer is free from interference by spironolactone, potassium canrenoate, and their common metabolite canrenone. Ther Drug Monit 2003; 25: 478–482.

    Article  PubMed  CAS  Google Scholar 

  5. Dai JL, Sokoll LJ, Chan DW. Automatedchemiluminescent immunoassay analyzers. J Clin Ligand Assay 1998; 21: 377–385.

    Google Scholar 

  6. MEIA Montagne P, Varcin P, Cuilliere ML, Duheille J. Microparticle-enhanced nephelometric immunoassay with microsphere-antigen conjugate. Bioconjugate Chem 1992; 3: 187–193.

    Article  Google Scholar 

  7. Datta P, Larsen F. Specificityof digoxin immunoassays toward digoxin metabolites. Clin Chem 1994; 40: 1348–1349.

    PubMed  CAS  Google Scholar 

  8. Datta P. Oxaprozinand 5-(p-hydroxyphenyl)-5-phenylhydantoin interference in phenytoin immunoassays. Clin Chem 1997; 43: 1468–1469.

    PubMed  CAS  Google Scholar 

  9. Datta P, Dasgupta A. Bidirectional(positive/negative) interference in a digoxin immunoassay: importance of antibody specificity. Ther Drug Monit 1998; 20: 352–357.

    Article  PubMed  CAS  Google Scholar 

  10. Mayer-Helm BX, Kahlig H, Rauter W. Tetramethyl-p,p’-sildiphenylene ether-dimethyl, diphenylsiloxane copolymer as stationary phase in gas chromatography. J Chromatogr A 2004; 1042: 147–154.

    Article  PubMed  CAS  Google Scholar 

  11. Gentil E, Banoub J. Characterizationand differentiation of isomeric self-complementary DNA oligomers by electrospray tandem mass spectrometry. J Mass Spectrom 1996; 31: 83–94.

    Article  PubMed  CAS  Google Scholar 

  12. Zancani M, Peresson C, Biroccio A, Federici G, et al. Evidencefor the presence of ferritin in plant mitochondria. Eur J Biochem 2004; 271: 3657–3664.

    Article  PubMed  CAS  Google Scholar 

  13. Marquet P, Lachatre G. Liquidchromatography-mass spectrometry in forensic and clinical toxicology. J Chromatogr B 1999; 7333: 93–118.

    Google Scholar 

  14. Taylor P. Therapeuticdrug monitoring of immunosuppressant drugs by high performance liquid chromatography-mass spectrometry. Ther Drug Monit 2004; 26: 215–219.

    Article  PubMed  CAS  Google Scholar 

  15. Napoli KL. Ismicroparticle enzyme-linked immunoassay (MEIA) reliable for use of tacrolimus TDM? Comparison of MEIA to liquid chromatography with mass spectrometric detection using longitudinal trough samples from transplant recipients. Ther Drug Monit 2006; 28: 491–504.

    Article  PubMed  CAS  Google Scholar 

  16. Kuperberg HJ. Quantitativeestimation of diphenylhydantoin, primidone and phenobarbital in plasma by gas liquid chromatography. Clin Chim Acta 1970; 29: 282–288.

    Google Scholar 

  17. Davis HL, Falk KJ, Bailey DG. Improvedmethod for the simultaneous determinations of Phenobarbital, primidone and diphenylhydantoin in patients’ serum by gas liquid chromatography. J Chromatogr 1975; 9: 61–66.

    Article  Google Scholar 

  18. Attwell SH, Green VA, Haney WG. Developmentand evaluation of method for simultaneous determination of phenobarbital and diphenylhydantoin in plasma by high pressure liquid chromatography. J Pharm Sci 1975; 64: 806–809.

    Article  Google Scholar 

  19. Dietzler DN, Hoelting CR, Leckie MP, Smith CH, et al. Emitassays for five major anticonvulsant drugs: an evaluation of adaptations to two discrete kinetic analyzers. Am J Clin Pathol 1980: 74: 41–50.

    PubMed  CAS  Google Scholar 

  20. Berg JD, Buckley BM. Rapidmeasurement of anticonvulsant drug concentrations in the out-patient clinic using HPLC with direct injection of plasma. Ann Clin Biochem 1987; 24: 488–493.

    PubMed  CAS  Google Scholar 

  21. Minkova G, Getova D. Determinationof carbamazepine and its metabolite carbamazepine 10, 11-epoxide in serum with gas chromatography mass spectrometry. Methods Find Exp Clin Pharmacol 2001; 23: 481–485.

    Article  PubMed  CAS  Google Scholar 

  22. Van Rooyen GF, Badenhorst D, Swart KJ, Hundt HK, et al. Determination of carbamazepine in human plasma by tandem liquid chromatography-mass spectrometry with electron spray ionization. J Chromatogr B Analyt Technol Biomed Life Sci 2002; 769: 1–7.

    Article  PubMed  Google Scholar 

  23. Bahrami G, Mohammadi B. Sensitivemicroanalysis of gabapentin by high performance liquid chromatography in human serum using pre column derivatization with 4-chloro-7-nitrobenzofuran: application to a bioequivalence study. J Chromatogr B Analyt Technol Biomed Life Sci 2006; 837: 24–28.

    Article  PubMed  CAS  Google Scholar 

  24. Contin M, Balboni M, Callegati E, Candela C, et al. Simultaneous liquid chromatographic determination of lamotrigine, oxcarbazepine monohydroxy derivative and felbamate in plasma of patients with epilepsy. J Chromatogr B Analyt Technol Biomed Life Sci 2005; 828: 113–117.

    Article  PubMed  CAS  Google Scholar 

  25. Dasgupta A, Hart AP. Lamotrigineanalysis in plasma by gas chromatography-mass spectrometry after conversion into a tert-butyldimethylsilyl derivative. J Chromatogr B Biomed Sci Appl 1997; 693: 101–107.

    Article  PubMed  CAS  Google Scholar 

  26. Berry D, Millington C. Analysisof pregabalin at therapeutic concentrations in human plasma/serum by reverse phase HPLC. Ther Drug Monit 2005; 27: 451–456.

    Article  PubMed  CAS  Google Scholar 

  27. Chen BH, Taylor EH, Pappas AA. Totaland free disopyramide by fluorescence polarization immunoassay and relationship between free fraction and alpha-1-acid glycoprotein. Clin Chim Acta 1987; 163: 75–90.

    Article  PubMed  CAS  Google Scholar 

  28. Shaw LM, Doherty JU, Waxman HL, Josephson ME. Thepharmacokinetic and pharmacodynamic effects of carrying the free fraction of disopyramide. Angiology 1987; 38: 192–197.

    PubMed  CAS  Google Scholar 

  29. Scislowski M, Rojek S, Klys M, Wozniak K, et al. Applicationof HPLC/MS for evaluation of fatal poisoning with digoxin in the aspect of medico-legal evidence. Arch Med Sadowej Kryminol 2002; 53: 19–31 [in Polish].

    Google Scholar 

  30. Verbesselt R, Tjandramaga TB, de Schepper PJ. Highperformance liquid chromatographic determination of 12 antiarrhythmic drugs in plasma using solid phase extraction. Ther Drug Monit 1991; 13: 157–165.

    Article  PubMed  CAS  Google Scholar 

  31. Dasgupta A, Rosenzweig IB, Turgeon J, Raisys VA. Encainideand metabolites analysis in serum or plasma using a reversed-phase high performance liquid chromatographic technique. J Chromatogr 1990; 526: 260–265.

    Article  PubMed  CAS  Google Scholar 

  32. vasBinder E, Annesley T. Liquidchromatographic analysis of mexiletine in serum with alternate application to tocainide, procainamide and N-acetylprocainamide. Biomed Chromatogr 1991; 5: 19–22.

    Article  PubMed  CAS  Google Scholar 

  33. McErlance KM, Igwemezie L, Kerr CR. Stereoselectiveanalysis of the enantiomers of mexiletine by high-performance liquid chromatography using fluorescence detection and study of stereoselective disposition in man. J Chromatogr 1987; 415: 335–346.

    Article  Google Scholar 

  34. Minnigh MB, Alvin JD, Zemaitis MA. Determinationof plasma mexiletine levels with gas chromatography-mass spectrometry and selected ion monitoring. J Chromatogr B Biomed Appl 1994; 662: 118–122.

    Article  PubMed  CAS  Google Scholar 

  35. Dasgupta A, Appenzeller P, Moore J. Gaschromatography-electron ionization mass spectrometric analysis of serum mexiletine concentration after derivatization with 2,2,2-trochloroethyl chloroformate: a novel derivative. Ther Drug Monit 1998; 20: 313–318.

    Article  PubMed  CAS  Google Scholar 

  36. Dasgupta A, Yousef O. Gaschromatographic-mass spectrometric determination of serum mexiletine concentration after derivatization with perfluorooctanoyl chloride, a new derivative. J Chromatogr B Biomed Sci Appl 1998; 705: 282–288.

    Article  Google Scholar 

  37. Doki K, Homma M, Kuga K, Watanabe S, et al. Simultaneous determination of serum flecainide and its metabolites by using high performance liquid chromatography. J Pharm Biomed Anal 2004; 35: 1307–1312.

    Article  PubMed  CAS  Google Scholar 

  38. Fischer C, Buhl K. Gaschromatography/mass spectrometry validation of high performance liquid chromatography analysis of flecainide enantiomers in serum. Ther Drug Monit 1992; 14: 433–435.

    Article  PubMed  CAS  Google Scholar 

  39. Dasgupta A, McNeese C, Wells A. Interferenceof carbamazepine and carbamazepine 10, 11-epoxide in the fluorescence polarization immunoassays for tricyclic antidepressants: estimation of true tricyclic antidepressant concentrations in the presence of carbamazepine using a mathematical model. Am J Clin Pathol 2004; 121: 418–423.

    Article  PubMed  CAS  Google Scholar 

  40. Chattergoon DS, Verjee Z, Anderson M, Johnson D, et al. Carbamazepine interference with an immune assay for tricyclic antidepressants in plasma. J Clin Toxicol 1998; 36: 109–113.

    Article  CAS  Google Scholar 

  41. Wille SM, Maudens KE, Van Peteghem CH, Lambert WE. Developmentof a solid phase extraction for 13 new generation antidepressants and their active metabolites for gas chromatographic-mass spectrometry analysis. J Chromatogr A 2005; 1098: 19–29.

    Article  PubMed  CAS  Google Scholar 

  42. Juan H, Zhiling Z, Huande L. Simultaneousdetermination of fluoxetine, citalopram, paroxetine, venlafaxine in plasma by high performance liquid chromatography-electrospray ionization mass spectrometry (HPLC-MS/ESI). J Chromatogr B Analyt Technol Biomed Life Sci 2005; 820: 33–39.

    Article  PubMed  CAS  Google Scholar 

  43. Isoherranen N, Soback S. Chromatographicmethods for analysis of aminoglycoside antibiotics. J AOAC Int 1999; 82: 1017–1045.

    PubMed  CAS  Google Scholar 

  44. Lai F, Sheehan T. Enhancedof detection sensitivity and cleanup selectivity for tobramycin through pre-column derivatization. J Chromatogr 1992; 609: 173–179.

    Article  PubMed  CAS  Google Scholar 

  45. Ovalles JF, Brunetto Mdel R, Gallignani M. Anew method for the analysis of amikacin using 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) derivatization and high performance liquid chromatography with UV detection. J Pharm Biomed Anal 2005; 39: 294–298.

    Article  PubMed  CAS  Google Scholar 

  46. Nicoli S, Santi P. Assayof amikacin in the skin by high performance liquid chromatography. J Pharm Biomed Anal 2006; 41: 994–997.

    Article  PubMed  CAS  Google Scholar 

  47. Kawamoto T, Mashimoto I, Yamauchi S, Watanabe M. Determinationof sisomicin, netilmicin, astromicin and micronomicin in serum by high-performance liquid chromatography. J Chromatogr 1984; 305: 373–379.

    PubMed  CAS  Google Scholar 

  48. Soltes L. Aminoglycosideantibiotics-two decades of their HPLC bioanalysis. Biomed Chromatogr 1999; 13: 3–10.

    Article  PubMed  CAS  Google Scholar 

  49. Galanakis EG, Megoulas NC, Solich P, Koupparis MA. Developmentand validation of a novel LC-non derivatization method for the determination of amikacin in pharmaceuticals based on evaporative light scattering detection. J Pharm Biomed Appl 2006; 40: 1114–1120.

    Article  CAS  Google Scholar 

  50. Kim BH, Lee SC, Lee HJ, Ok JH. Reversed-phase liquid chromatographic method for the analysis of aminoglycoside antibiotics using pre-column derivatization with phenylisocyanate. Biomed Chromatogr 2003; 17: 396–403.

    Article  PubMed  CAS  Google Scholar 

  51. Sagan C, Salvador A, Dubreuil D, Poulet PP, et al. Simultaneous determination of metronidazole and spiramycin in human plasma, saliva and gingival crevicular fluid by LC-MS/MS. J Pharm Biomed Anal 2005; 38:298–306.

    Article  PubMed  CAS  Google Scholar 

  52. Lee JW, Peterson ME, Lin P, Dressler D, et al. Quantitationof free and total amphotericin B in human biologic matrices by a liquid chromatography tandem mass spectrometric method. Ther Drug Monit 2001; 23: 268–276.

    Article  PubMed  CAS  Google Scholar 

  53. Fouda HG, Schneider RP. Quantitativedetermination of the antibiotic azithromycin in human serum by high performance liquid chromatography (HPLC)-atmospheric pressure chemical ionization mass spectrometry: correlation with a standard HPLC electrochemical method. Ther Drug Monit 1995; 17: 179–183.

    Article  PubMed  CAS  Google Scholar 

  54. Truci R, Fiorentino ML, Sottani C, Minoia C. Determinationof methotrexate in human urine trace levels by solid phase extraction and high performance liquid chromatography/tandem mass spectrometry. Rapid Commun Mass Spectrom 2000; 14: 173–179.

    Article  Google Scholar 

  55. el-Yazigi A, Ezzat A. Pharmacokineticmonitoring of anticancer drugs at King Faisal Specialist Hospital, Riyadh, Saudi Arabia. Ther Drug Monit 1997; 19: 390–393.

    Article  PubMed  CAS  Google Scholar 

  56. Maring JG, Schouten L, Greijdanus B, de Vries EG, et al. Asimple and sensitive fully validated HPLC-UV method for the determination of 5-fluorouracil and its metabolite 5, 6-dihydrofluorouracil in plasma. Ther Drug Monit 2005; 27: 25–30.

    Article  PubMed  CAS  Google Scholar 

  57. Schoemaker NE, Rosing H, Jansen S, Schellens JH, et al. High performance liquid chromatographic analysis of the anticancer drug irinotecan (CPT-11) and its active metabolite SN-38 in human plasma. Ther Drug Monit 2003; 25: 120–124.

    Article  PubMed  CAS  Google Scholar 

  58. Zufia Lopez L, Aldaz Pastor A, Armendia Beitia JM, Arrobas Velilla J, et al. Determinationof docetaxel and paclitaxel in human plasma by high performance liquid chromatography: validation and application to clinical pharmacokinetic studies. Ther Drug Monit 2006; 28: 199–205.

    Article  PubMed  CAS  Google Scholar 

  59. Titier K, Picard S, Ducint D, Teihet E, et al. Quantificationof imatinib in human plasma by high performance liquid chromatography-tandem mass spectrometry. Ther Drug Monit 2005; 27: 634–640.

    Article  PubMed  CAS  Google Scholar 

  60. Fogil S, Danesi R, Innocenti F, Di Paolo A, et al. Animproved HPLC method for therapeutic drug monitoring of daunorubicin, idarubicin, doxorubicin, epirubicin and their 13-dihydro metabolites in human plasma. Ther Drug Monit 1999; 21: 367–375.

    Article  Google Scholar 

  61. Lachatre F, Marquet P, Ragot S, Gaulier JM, et al. Simultaneous determination of four anthracyclines and three active metabolites in human serum by liquid chromatography-electrospray mass spectrometry. J Chromatogr B Biomed Sci Appl 2000; 738: 281–291.

    Article  PubMed  CAS  Google Scholar 

  62. Kerbusch T, Jeuken MJ, Derraz J, van Putten JW, et al. Determination of ifosfamide, 2 and 3-dechloroethylifosfamide using gas chromatography with nitrogen-phosphorus or mass spectrometry detection. Ther Drug Monit 2000; 22: 613–620.

    Article  PubMed  CAS  Google Scholar 

  63. Sampson M, Ruddel M, Elin RJ. Lithiumdetermination evaluated in eight analyzers. Clin Chem 1994; 40: 869–872.

    PubMed  CAS  Google Scholar 

  64. Christian GD. Analyticalstrategies for the measurement of lithium in biological samples. J Pharm Biomed Anal 1996; 14: 899–908.

    Article  PubMed  CAS  Google Scholar 

  65. Kloft C, Appelius H, Siegert W, Schunack W, et al. Determinationof platinum complexes in clinical samples by a rapid flameless absorption spectrometry assay. Ther Drug Monit 1999; 21: 631–637.

    Article  PubMed  CAS  Google Scholar 

  66. Wong SH. Supercriticalfluid chromatography and microbore liquid chromatography for drug analysis. Clin Chem 1989: 35: 1293–1298.

    PubMed  CAS  Google Scholar 

  67. Graves SW, Markides KE, Hollenberg NK. Applicationof supercritical fluid chromatography to characterize a labile digitalis-like factor. Hypertension 2000; 36: 1059–1064.

    PubMed  CAS  Google Scholar 

  68. Thormann W, Zhang CX, Schmutz A. Capillaryelectrophoresis for drug analysis in body fluid. Ther Drug Monit 1996; 18: 506–520.

    Article  PubMed  CAS  Google Scholar 

  69. Teshima D, Otsubo K, Makino K, Itoh Y, et al. Simultaneous determination of sulfamethoxazole and trimethoprim in human plasma by capillary zone electrophoresis. Biomed Chromatogr 2004; 18: 51–54.

    Article  PubMed  CAS  Google Scholar 

  70. Rodriguez Flores J, Penalvo GC, Mansilla AE, Gomez MJ. Capillary zone electrophoresis determination of methotrexate, leucovorin and folic acid in human urine. J Chromatogr B Analyt Technol Biomed Life Sci 2005; 819: 141–147.

    Article  PubMed  CAS  Google Scholar 

  71. Zheng J, Jann MW, Hon YY, Shamsi SA. Developmentof capillary zone electrophoresis-electrospray ionization mass spectrometry for the determination of lamotrigine in human plasma. Electrophoresis 2004; 25: 2033–2043.

    Article  PubMed  CAS  Google Scholar 

  72. Fonge H, Kaale E, Govaerts C, Desmet K, et al. Bioanalysisof tobramycin for therapeutic drug monitoring by solid phase extraction and capillary zone electrophoresis. J Chromatogr B Analyt Technol Biomed Life Sci 2004; 810: 313–318.

    Article  PubMed  CAS  Google Scholar 

  73. Makino K, Itoh Y, Teshima D, Oishi R. Determinationof nonsteroidal anti-inflammatory drugs in human specimens by capillary zone electrophoresis and micellar electrokinetic chromatography. Electrophoresis 2004; 25: 1488–1495.

    Article  PubMed  CAS  Google Scholar 

  74. Huang Z, Timerbaev AR, Keppler BK, Hirokawa T. Determinationof cisplatin and its hydrolytic metabolite in human serum by capillary electrophoresis technique. J Chromatogr A 2006; 1106: 75–79.

    Article  PubMed  CAS  Google Scholar 

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Authors
  1. Amitava Dasgupta PhD
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  2. Pradip Datta PhD
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Editors and Affiliations

  1. Department of Pathology and Laboratory Medicine, University of Texas-Houston Medical School, Houston, TX

    Amitava Dasgupta PhD,DABCC,FACB

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Dasgupta, A., Datta, P. (2008). Analytical Techniques for Measuring Concentrations of Therapeutic Drugs in Biological Fluids. In: Dasgupta, A. (eds) Handbook of Drug Monitoring Methods. Humana Press. https://doi.org/10.1007/978-1-59745-031-7_3

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  • DOI: https://doi.org/10.1007/978-1-59745-031-7_3

  • Publisher Name: Humana Press

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  • Online ISBN: 978-1-59745-031-7

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