Skip to main content

Advertisement

SpringerLink
Log in

Cross-validation of a mass spectrometric-based method for the therapeutic drug monitoring of irinotecan: implementation of matrix-assisted laser desorption/ionization mass spectrometry in pharmacokinetic measurements

  • Research Paper
  • Published:
Analytical and Bioanalytical Chemistry Aims and scope Submit manuscript

Abstract

Irinotecan is a widely used antineoplastic drug, mostly employed for the treatment of colorectal cancer. This drug is a feasible candidate for therapeutic drug monitoring due to the presence of a wide inter-individual variability in the pharmacokinetic and pharmacodynamic parameters. In order to determine the drug concentration during the administration protocol, we developed a quantitative MALDI-MS method using CHCA as MALDI matrix. Here, we demonstrate that MALDI-TOF can be applied in a routine setting for therapeutic drug monitoring in humans offering quick and accurate results. To reach this aim, we cross validated, according to FDA and EMA guidelines, the MALDI-TOF method in comparison with a standard LC-MS/MS method, applying it for the quantification of 108 patients’ plasma samples from a clinical trial. Standard curves for irinotecan were linear (R 2 ≥ 0.9842) over the concentration ranges between 300 and 10,000 ng/mL and showed good back-calculated accuracy and precision. Intra- and inter-day precision and accuracy, determined on three quality control levels were always <12.8 % and between 90.1 and 106.9 %, respectively. The cross-validation procedure showed a good reproducibility between the two methods, the percentage differences within 20 % in more than 70 % of the total amount of clinical samples analysed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. de Jonge ME, Huitema AD, Schellens JH, Rodenhuis S, Beijnen JH. Individualised cancer chemotherapy: strategies and performance of prospective studies on therapeutic drug monitoring with dose adaptation: a review. Clin Pharmacokinet. 2005;44(2):147–73.

    Article  Google Scholar 

  2. Widmer N, Bardin C, Chatelut E, Paci A, Beijnen J, Leveque D, et al. Review of therapeutic drug monitoring of anticancer drugs part two—targeted therapies. Eur J Cancer. 2014;50(12):2020–36.

    Article  CAS  Google Scholar 

  3. Paci A, Veal G, Bardin C, Leveque D, Widmer N, Beijnen J, et al. Review of therapeutic drug monitoring of anticancer drugs part 1—cytotoxics. Eur J Cancer. 2014;50(12):2010–9.

    Article  CAS  Google Scholar 

  4. Saint-Marcoux F, Sauvage FL, Marquet P. Current role of LC-MS in therapeutic drug monitoring. Anal Bioanal Chem. 2007;388(7):1327–49.

    Article  CAS  Google Scholar 

  5. Muddiman DC, Gusev AI, Proctor A, Hercules DM, Venkataramanan R, Diven W. Quantitative measurement of cyclosporin A in blood by time-of-flight mass spectrometry. Anal Chem. 1994;66(14):2362–8.

    Article  CAS  Google Scholar 

  6. Muddiman DC, Gusev AI, Martin LB, Hercules DM. Direct quantification of cocaine in urine by time-of-flight mass spectrometry. Fresen J Anal Chem. 1996;354(1):103–10.

    Article  CAS  Google Scholar 

  7. Muddiman DC, Gusev AI, Karl Stoppek L, Proctor A, Hercules DM, Tata P, et al. Simultaneous quantification of cyclosporin A and its major metabolites by time-of-flight secondary-ion mass spectrometry and matrix-assisted laser desorption/ionization mass spectrometry utilizing data analysis techniques: comparison with high-performance liquid chromatography. J Mass Spectrom. 1995;30(10):1469–79.

    Article  CAS  Google Scholar 

  8. Zhao YP, Lam M, Wu DL, Mak R. Quantification of small molecules in plasma with direct analysis in real time tandem mass spectrometry, without sample preparation and liquid chromatographic separation. Rapid Commun Mass Spectrom. 2008;22(20):3217–24.

    Article  CAS  Google Scholar 

  9. Yu S, Crawford E, Tice J, Musselman B, Wu JT. Bioanalysis without sample cleanup or chromatography: the evaluation and initial implementation of direct analysis in real time ionization mass spectrometry for the quantification of drugs in biological matrixes. Anal Chem. 2009;81(1):193–202.

    Article  CAS  Google Scholar 

  10. Crawford E, Gordon J, Wu JT, Musselman B, Liu R, Yu S. Direct analysis in real time coupled with dried spot sampling for bioanalysis in a drug-discovery setting. Bioanalysis. 2011;3(11):1217–26.

    Article  CAS  Google Scholar 

  11. Espy RD, Manicke NE, Ouyang Z, Cooks RG. Rapid analysis of whole blood by paper spray mass spectrometry for point-of-care therapeutic drug monitoring. Analyst (Cambridge, U K). 2012;137(10):2344–9.

    Article  CAS  Google Scholar 

  12. Su Y, Wang H, Liu J, Wei P, Cooks RG, Zheng O. Quantitative paper spray mass spectrometry analysis of drugs of abuse. The Analyst. 2013;138(16):4443–7.

    Article  CAS  Google Scholar 

  13. Duncan MW, Matanovic G, Cerpapoljak A. Quantitative-analysis of low-molecular-weight compounds of biological interest by matrix-assisted laser-desorption ionization. Rapid Commun Mass Spectrom. 1993;7(12):1090–4.

    Article  CAS  Google Scholar 

  14. Calandra E, Crotti S, Agostini M, Nitti D, Roverso M, Toffoli G, et al. Matrix-assisted laser desorption/ionization, nanostructure-assisted laser desorption/ionization and carbon nanohorns in the detection of antineoplastic drugs. 1. The cases of irinotecan, sunitinib and 6-alpha-hydroxy paclitaxel. Eur J Mass Spectrom (Chichester, Eng). 2014;20(6):445–59.

    Article  CAS  Google Scholar 

  15. Calandra E, Crotti S, Nitti D, Roverso M, Toffoli G, Marangon E, et al. The development of a matrix-assisted laser desorption/ionization (MALDI)-based analytical method for determination of irinotecan levels in human plasma: preliminary results. J Mass Spectrom. 2015;50(7):959–62.

    Article  CAS  Google Scholar 

  16. van Kampen JJ, Burgers PC, de Groot R, Luider TM. Qualitative and quantitative analysis of pharmaceutical compounds by MALDI-TOF mass spectrometry. Anal Chem. 2006;78(15):5403–11.

    Article  Google Scholar 

  17. Gusev AI, Muddiman DC, Proctor A, Sharkey AG, Hercules DM, Tata PNV, et al. A quantitative study of in vitro hepatic metabolism of Tacrolimus (FK506) using secondary ion and matrix-assisted laser desorption/ionization mass spectrometry. Rapid Commun Mass Spectrom. 1996;10(10):1215–8.

    Article  CAS  Google Scholar 

  18. Shaaban H, Gorecki T. Current trends in green liquid chromatography for the analysis of pharmaceutically active compounds in the environmental water compartments. Talanta. 2015;132:739–52.

    Article  CAS  Google Scholar 

  19. Bucknall M, Fung KYC, Duncan MW. Practical quantitative biomedical applications of MALDI-TOF mass spectrometry. J Am Soc Mass Spectr. 2002;13(9):1015–27.

    Article  CAS  Google Scholar 

  20. Duncan MW, Roder H, Hunsucker SW. Quantitative matrix-assisted laser desorption/ionization mass spectrometry. Brief Funct Genomic Proteomic. 2008;7(5):355–70.

    Article  CAS  Google Scholar 

  21. Molin L, Cristoni S, Crotti S, Bernardi LR, Seraglia R, Traldi P. Sieve-based device for MALDI sample preparation. I. Influence of sample deposition conditions in oligonucleotide analysis to achieve significant increases in both sensitivity and resolution. J Mass Spectrom. 2008;43(11):1512–20.

    Article  CAS  Google Scholar 

  22. Cristoni S, Molin L, Crotti S, Bernardi LR, Seraglia R, Traldi P. Sieve-based device for MALDI sample preparation. II. Instrumental parameterization. J Mass Spectrom. 2009;44(11):1579–86.

    Article  CAS  Google Scholar 

  23. Innocenti F, Undevia SD, Iyer L, Chen PX, Das S, Kocherginsky M, et al. Genetic variants in the UDP-glucuronosyltransferase 1A1 gene predict the risk of severe neutropenia of irinotecan. J Clin Oncol. 2004;22(8):1382–8.

    Article  CAS  Google Scholar 

  24. Tlsty TD. Stromal cells can contribute oncogenic signals. Semin Cancer Biol. 2001;11(2):97–104.

    Article  CAS  Google Scholar 

  25. European Medicines Agency Committee for Medicinal Products for Human Use (CHMP) Guideline on bioanalytical method validation. 2011 [02/11/2015]; Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2011/08/WC500109686.pdf.

  26. Marangon E, Posocco B, Mazzega E, Toffoli G. Development and validation of a high-performance liquid chromatography-tandem mass spectrometry method for the simultaneous determination of irinotecan and its main metabolites in human plasma and its application in a clinical pharmacokinetic study. PLoS One. 2015;10(2), e0118194.

    Article  Google Scholar 

  27. U.S. Food and Drug Administration Center for Drug Evaluation and Research (CDER) guidance for industry bioanalytical method validation. 2001 [02/11/2015]; Available from: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM070107.pdf.

  28. FDA. U.S. Food and Drug Administration Center for Drug Evaluation and Research (CDER) Guidance for industry bioanalytical method validation. 2001; Available from: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM070107.pdf.

Download references

Acknowledgments

This work was supported in part by the Associazione Italiana Ricerca sul Cancro (AIRC) 5x1000 (grant n. 12214) and in part by the “Grant Program for Young Investigator on Paediatric Research” 2013 from Fondazione CARIPARO.

Author information

Authors and Affiliations

  1. Lab. NIB, Pediatric Research Institute, Città della Speranza, Corso Stati Uniti 4, 35127, Padua, Italy

    Eleonora Calandra, Sara Crotti, Pietro Traldi & Marco Agostini

  2. Experimental and Clinical Pharmacology Division, Department of Translational Research, IRCCS-National Cancer Institute, Via Franco Gallini 2, 33081, Aviano, Italy

    Bianca Posocco, Elena Marangon, Luciana Giodini & Giuseppe Toffoli

  3. Surgical Clinic, Department of Surgical, Oncological and Gastroenterological Sciences, University of Padova, Via Nicolo Giustiniani 2, 35128, Padua, Italy

    Donato Nitti & Marco Agostini

  4. IENI CNR, Corso Stati Uniti 4, 35127, Padua, Italy

    Pietro Traldi

  5. Department of Nanomedicine, The Methodist Hospital Research Institute, 6670 Bertner Avenue, Houston, TX, 77030, USA

    Marco Agostini

Authors
  1. Eleonora Calandra
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bianca Posocco
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sara Crotti
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Elena Marangon
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Luciana Giodini
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Donato Nitti
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Giuseppe Toffoli
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Pietro Traldi
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Marco Agostini
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sara Crotti.

Ethics declarations

This study was conducted according to the principles expressed in the Declaration of Helsinki. All blood samples were collected under the full ethical approval of the ethics committee of the participating centres and only after the signature of informed consent from all the enrolled patients.

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Calandra, E., Posocco, B., Crotti, S. et al. Cross-validation of a mass spectrometric-based method for the therapeutic drug monitoring of irinotecan: implementation of matrix-assisted laser desorption/ionization mass spectrometry in pharmacokinetic measurements. Anal Bioanal Chem 408, 5369–5377 (2016). https://doi.org/10.1007/s00216-016-9634-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-016-9634-5

Keywords

Search

Navigation