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Dried Blood Spot Technique Applied in Therapeutic Drug Monitoring of Anticancer Drugs: a Review on Conversion Methods to Correlate Plasma and Dried Blood Spot Concentrations

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Abstract

Background

Anticancer drugs are notoriously characterized by a low therapeutic index, the introduction of therapeutic drug monitoring (TDM) in oncologic clinical practice could therefore be fundamental to improve treatment efficacy. In this context, an attractive technique to overcome the conventional venous sampling limits and simplify TDM application is represented by dried blood spot (DBS). Despite the significant progress made in bioanalysis exploiting DBS, there is still the need to tackle some challenges that limit the application of this technology: one of the main issues is the comparison of drug concentrations obtained from DBS with those obtained from reference matrix (e.g., plasma). In fact, the use of DBS assays to estimate plasma concentrations is highly dependent on the chemical-physical characteristics of the measured analyte, in particular on how these properties determine the drug partition in whole blood.

Methods

In the present review, we introduce a critical investigation of the DBS-to-plasma concentration conversion methods proposed in the last ten years and applied to quantitative bioanalysis of anticancer drugs in DBS matrix. To prove the concordance between DBS and plasma concentration, the results of statistical tests applied and the presence or absence of trends or biases were also considered.

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References

  1. Gao B, Yeap S, Clements A, Balakrishnar B, Wong M, Gurney H. Evidence for therapeutic drug monitoring of targeted anticancer therapies. J Clin Oncol. 2012 Nov 10;30(32):4017–25.

    Article  CAS  PubMed  Google Scholar 

  2. Shenfield GM, Morris RG. Therapeutic drug monitoring. Curr Opin Anaesthesiol. 2002 Dec;15(6):687–92.

    Article  PubMed  Google Scholar 

  3. Bardin C, Veal G, Paci A, Chatelut E, Astier A, Levêque D, et al. Therapeutic drug monitoring in cancer – are we missing a trick? Eur J Cancer. 2014 Aug;50(12):2005–9.

    Article  CAS  PubMed  Google Scholar 

  4. Guthrie R, Susi A. A simple phenylalanine method for detecting phenylketonuria in large populations of newborn infants. Pediatrics. 1963 Sep 1;32(3):338–43.

    Article  CAS  PubMed  Google Scholar 

  5. Li W, Zhang J, Tse FLS. Strategies in quantitative LC-MS/MS analysis of unstable small molecules in biological matrices. Biomed Chromatogr. 2011 Jan;25(1–2):258–77.

    Article  PubMed  CAS  Google Scholar 

  6. Timmerman P, White S, Globig S, Lüdtke S, Brunet L, Smeraglia J. EBF recommendation on the validation of bioanalytical methods for dried blood spots. Bioanalysis. 2011 Jul;3(14):1567–75.

    Article  CAS  PubMed  Google Scholar 

  7. Capiau S, Veenhof H, Koster RA, Bergqvist Y, Boettcher M, Halmingh O, et al. Official International Association for Therapeutic Drug Monitoring and Clinical Toxicology Guideline: development and validation of dried blood spot–based methods for therapeutic drug monitoring. Ther Drug Monit. 2019;41(4):22.

    Article  CAS  Google Scholar 

  8. Sulochana SP, Daram P, Srinivas NR, Mullangi R. Review of DBS methods as a quantitative tool for anticancer drugs. Biomed Chromatogr. 2019;33(1):e4445.

    Article  PubMed  CAS  Google Scholar 

  9. Damen CWN, Rosing H, Schellens JHM, Beijnen JH. Application of dried blood spots combined with high-performance liquid chromatography coupled with electrospray ionisation tandem mass spectrometry for simultaneous quantification of vincristine and actinomycin-D. Anal Bioanal Chem. 2009 Jun;394(4):1171–82.

    Article  CAS  PubMed  Google Scholar 

  10. Nijenhuis CM, Rosing H, Schellens JH, Beijnen JH. Quantifying vemurafenib in dried blood spots using high-performance LC–MS/MS. Bioanalysis. 2014 Dec;6(23):3215–24.

    Article  CAS  PubMed  Google Scholar 

  11. Tré-Hardy M, Capron A, Antunes MV, Linden R, Wallemacq P. Fast method for simultaneous quantification of tamoxifen and metabolites in dried blood spots using an entry level LC–MS/MS system. Clin Biochem. 2016 Nov;49(16–17):1295–8.

    Article  PubMed  CAS  Google Scholar 

  12. Knapen LM, de Beer Y, Brüggemann RJM, Stolk LM, de Vries F, Tjan-Heijnen VCG, et al. Development and validation of an analytical method using UPLC–MS/MS to quantify everolimus in dried blood spots in the oncology setting. J Pharm Biomed Anal. 2018 Feb;149:106–13.

    Article  CAS  PubMed  Google Scholar 

  13. Xie F, De Thaye E, Vermeulen A, Van Bocxlaer J, Colin P. A dried blood spot assay for paclitaxel and its metabolites. J Pharm Biomed Anal. 2018 Jan;148:307–15.

    Article  CAS  PubMed  Google Scholar 

  14. Jager NG, Rosing H, Schellens JH, Beijnen JH. Determination of tamoxifen and endoxifen in dried blood spots using LC–MS/MS and the effect of coated DBS cards on recovery and matrix effects. Bioanalysis. 2014 Nov;6(22):2999–3009.

    Article  CAS  PubMed  Google Scholar 

  15. Koster RA, Veenhof H, Botma R, Hoekstra AT, Berger SP, Bakker SJ, et al. Dried blood spot validation of five immunosuppressants, without hematocrit correction, on two LC–MS/MS systems. Bioanalysis. 2017 Apr;9(7):553–63.

    Article  CAS  PubMed  Google Scholar 

  16. Lampič K, Trontelj J, Prosen H, Drobne D, Šmid A, Vovk T. Determination of 6-thioguanine and 6-methylmercaptopurine in dried blood spots using liquid chromatography-tandem mass spectrometry: method development, validation and clinical application. Clin Chim Acta. 2019 Dec;499:24–33.

    Article  PubMed  CAS  Google Scholar 

  17. Torres L-M, Rivera-Espinosa L, Chávez-Pacheco JL, Navas CF, Demetrio JA, Alemón-Medina R, et al. A new method to quantify ifosfamide blood levels using dried blood spots and UPLC-MS/MS in paediatric patients with embryonic solid tumours. Loeb DM, editor. PLoS ONE. 2015 Nov 23;10(11):e0143421.

  18. Hawwa AF, AlBawab A, Rooney M, Wedderburn LR, Beresford MW, McElnay JC. A novel dried blood spot-LCMS method for the quantification of methotrexate polyglutamates as a potential marker for methotrexate use in children. D’Incalci M, editor. PLoS ONE. 2014 Feb 25;9(2):e89908.

  19. Singhal P, Shah PA, Shah JV, Sharma P, Shrivastav PS. determination of capecitabine-an anticancer drug in dried blood spot by Lc-Esi-Ms/Ms. 7(12):8.

  20. Ansari M, Uppugunduri CRS, Déglon J, Théorêt Y, Versace F, Gumy-Pause F, et al. A simplified method for busulfan monitoring using dried blood spot in combination with liquid chromatography/tandem mass spectrometry. Rapid Commun Mass Spectrom. 2012 Jun 30;26(12):1437–46.

    Article  CAS  PubMed  Google Scholar 

  21. Supandi S, Harahap Y, Harmita H, Andalusia R. Quantification of 6-Mercaptopurine and its metabolites in patients with acute lympoblastic leukemia using dried blood spots and UPLC-MS/MS. Sci Pharm [Internet]. 2018 [cited 2021 Feb 13];86(2). Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6027686/

  22. P. S. S, Vijay Kumar S, Kumar A, Mullangi R. Development of an LC-MS/MS method for determination of bicalutamide on dried blood spots: application to pharmacokinetic study in mice: LC-MS/MS determination of bicalutamide in DBS. Biomed Chromatogr 2015 Feb;29(2):254–260.

  23. Nageswara Rao R, Satyanarayana Raju S, Mastan Vali R, Sarma VUM, Girija SG. LC-ESI-MS/MS determination of paclitaxel on dried blood spots. Biomed Chromatogr. 2012;26(5):616–21.

  24. Patro VJ. LC-MS/MS Determintion of cabazitaxel in rat whole blood on dry Blood Spots. 2012;1(6):4.

  25. Saini NK, Sulochana SP, Zainuddin M, Mullangi R. Development and validation of a novel method for simultaneous quantification of enzalutamide, darolutamide and their active metabolites in mice dried blood spots using LC-MS/MS: application to pharmacokinetic study in mice 2018;16.

  26. Saini NK, Sulochana SP, Kiran V, Zainuddin M, Mullangi R. A novel dried blood spot LC-MS/MS method for the quantification of apalutamide in mouse whole blood: application to pharmacokinetic study in mice. Biomed Chromatogr. 2018 Nov;32(11):e4344.

    Article  PubMed  CAS  Google Scholar 

  27. van der Heijden J, de Beer Y, Hoogtanders K, Christiaans M, de Jong GJ, Neef C, et al. Therapeutic drug monitoring of everolimus using the dried blood spot method in combination with liquid chromatography–mass spectrometry. J Pharm Biomed Anal. 2009 Nov;50(4):664–70.

    Article  PubMed  CAS  Google Scholar 

  28. Willemsen AECAB, Knapen LM, de Beer YM, Brüggemann RJM, Croes S, van Herpen CML, et al. Clinical validation study of dried blood spot for determining everolimus concentration in patients with cancer. Eur J Clin Pharmacol. 2018 Apr;74(4):465–71.

    Article  CAS  PubMed  Google Scholar 

  29. Verheijen RB, Thijssen B, Atrafi F, Schellens JHM, Rosing H, de Vries N, et al. Validation and clinical application of an LC-MS/MS method for the quantification of everolimus using volumetric absorptive microsampling. J Chromatogr B. 2019 Jan;1104:234–9.

    Article  CAS  Google Scholar 

  30. Veenhof H, Koster RA, Alffenaar J-WC, van den Berg AP, de Groot MR, Verschuuren EAM, et al. Clinical application of a dried blood spot assay for sirolimus and everolimus in transplant patients. Clinical Chemistry and Laboratory Medicine (CCLM). 2019 Nov 26;57(12):1854–62.

    Article  CAS  Google Scholar 

  31. Matsumoto K, Uchida N, Sakurai A, Taniguchi S, Morita K. Clinical application of the dried blood spot method in the measurement of blood Busulfan concentration. Biology of Blood and Marrow Transplantation. 2016 Nov;22(11):1968–73.

    Article  CAS  PubMed  Google Scholar 

  32. Dilo A, Daali Y, Desmeules J, Chalandon Y, Uppugunduri CRS, Ansari M. Comparing dried blood spots and plasma concentrations for Busulfan therapeutic drug monitoring in children. Ther Drug Monit. 2020 Feb;42(1):111–7.

    Article  CAS  PubMed  Google Scholar 

  33. Režonja Kukec R, Grabnar I, Mrhar A, Čebron Lipovec N, Čufer T, Vovk T. A simple dried blood spot method for clinical pharmacological analyses of etoposide in cancer patients using liquid chromatography and fluorescence detection. Clin Chim Acta. 2016 Jan;452:99–105.

    Article  PubMed  CAS  Google Scholar 

  34. Jager NGL, Rosing H, Schellens JHM, Beijnen JH, Linn SC. Use of dried blood spots for the determination of serum concentrations of tamoxifen and endoxifen. Breast Cancer Res Treat. 2014 Jul;146(1):137–44.

    Article  CAS  PubMed  Google Scholar 

  35. Antunes MV, Raymundo S, de Oliveira V, Staudt DE, Gössling G, Peteffi GP, et al. Ultra-high performance liquid chromatography tandem mass spectrometric method for the determination of tamoxifen, N -desmethyltamoxifen, 4-hydroxytamoxifen and endoxifen in dried blood spots—development, validation and clinical application during breast cancer adjuvant therapy. Talanta. 2015 Jan;132:775–84.

    Article  CAS  PubMed  Google Scholar 

  36. Hahn RZ, Arnhold PC, Andriguetti NB, Schneider A, Klück HM, dos Reis SL, et al. Determination of irinotecan and its metabolite SN-38 in dried blood spots using high-performance liquid-chromatography with fluorescence detection. J Pharm Biomed Anal. 2018 Feb;150:51–8.

    Article  CAS  PubMed  Google Scholar 

  37. Nijenhuis CM, Huitema ADR, Marchetti S, Blank C, Haanen JBAG, van Thienen JV, et al. The use of dried blood spots for pharmacokinetic monitoring of Vemurafenib treatment in melanoma patients. J Clin Pharmacol. 2016;56(10):1307–12.

    Article  CAS  PubMed  Google Scholar 

  38. Andriguetti NB, Hahn RZ, Lizot LF, Raymundo S, Costa JL, da Cunha KF, et al. Analytical and clinical validation of a dried blood spot assay for the determination of paclitaxel using high-performance liquid chromatography-tandem mass spectrometry. Clin Biochem. 2018 Apr;54:123–30.

    Article  CAS  PubMed  Google Scholar 

  39. Raymundo S, Muller VV, Andriguetti NB, Tegner M, Artmann AC, Kluck HM, et al. Determination of docetaxel in dried blood spots by LC–MS/MS: method development, validation and clinical application. J Pharm Biomed Anal. 2018 Aug;157:84–91.

    Article  CAS  PubMed  Google Scholar 

  40. Kralj E, Trontelj J, Paji T, Kristl A. Simultaneous measurement of imatinib, nilotinib and dasatinib in dried blood spot by ultra high performance liquid chromatography tandem mass spectrometry. J Chromatogr B. 2012 Aug;903:150–6.

    Article  CAS  Google Scholar 

  41. Antunes MV, Raymundo S, Wagner SC, Mattevi VS, Vieira N, Leite R, et al. DBS sampling in imatinib therapeutic drug monitoring: from method development to clinical application. Bioanalysis. 2015 Sep;7(16):2105–17.

    Article  CAS  PubMed  Google Scholar 

  42. Iacuzzi V, Posocco B, Zanchetta M, Montico M, Marangon E, Poetto AS, et al. Development and validation of LC-MS/MS method for imatinib and norimatinib monitoring by finger-prick DBS in gastrointestinal stromal tumor patients. PLoS One. 2019;14(11):e0225225.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Boons CCLM, Chahbouni A, Schimmel AM, Wilhelm AJ, den Hartog YM, Janssen JJWM, et al. Dried blood spot sampling of nilotinib in patients with chronic myeloid leukaemia: a comparison with venous blood sampling. J Pharm Pharmacol. 2017 Oct;69(10):1265–74.

    Article  CAS  PubMed  Google Scholar 

  44. de Wit D, den Hartigh J, Gelderblom H, Qian Y, den Hollander M, Verheul H, et al. Dried blood spot analysis for therapeutic drug monitoring of pazopanib. J Clin Pharmacol. 2015 Dec;55(12):1344–50.

    Article  PubMed  CAS  Google Scholar 

  45. Verheijen RB, Bins S, Thijssen B, Rosing H, Nan L, Schellens JH, et al. Development and clinical validation of an LC–MS/MS method for the quantification of pazopanib in DBS. Bioanalysis. 2016 Jan;8(2):123–34.

    Article  CAS  PubMed  Google Scholar 

  46. Irie K, Shobu S, Hiratsuji S, Yamasaki Y, Nanjo S, Kokan C, et al. Development and validation of a method for gefitinib quantification in dried blood spots using liquid chromatography-tandem mass spectrometry: application to finger-prick clinical blood samples of patients with non-small cell lung cancer. J Chromatogr B. 2018 Jun;1087–1088:1–5.

    Article  CAS  Google Scholar 

  47. Lee J, Jung SY, Choi M, Park J, Park S, Lim S, et al. Development of a dried blood spot sampling method towards therapeutic monitoring of radotinib in the treatment of chronic myeloid leukaemia. J Clin Pharm Ther. 2020 Oct;45(5):1006–13.

    Article  CAS  PubMed  Google Scholar 

  48. Enderle Y, Foerster K, Burhenne J. Clinical feasibility of dried blood spots: analytics, validation, and applications. J Pharm Biomed Anal. 2016 Oct;130:231–43.

    Article  CAS  PubMed  Google Scholar 

  49. FDA. Bioanalytical Method Validation Guidance for Industry. 2018;2018:44.

    Google Scholar 

  50. EMA. Guideline on bioanalytical method validation. 2011.

  51. PMDA. Guideline on Bioanalytical Method Validation in Pharmaceutical Development [Internet]. 2013 [cited 2021 Feb 19]. Available from: https://www.pmda.go.jp/files/000206209.pdf

  52. Measurement Procedure Comparison and Bias Estimation Using Patient Samples; Approved Guideline - 3rd Edition (EP09-A3 | AACC.org [Internet]. [cited 2021 Jan 27]. Available from: https://www.aacc.org/store/books/9200/measurement-procedure-comparison-and-bias-estimation-using-patient-samples

  53. Emmons G, Rowland M. Pharmacokinetic considerations as to when to use dried blood spot sampling. Bioanalysis. 2010 Nov;2(11):1791–6.

    Article  CAS  PubMed  Google Scholar 

  54. Rowland M, Emmons GT. Use of dried blood spots in drug development: pharmacokinetic considerations. AAPS J. 2010 Sep;12(3):290–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. De Kesel PM, Sadones N, Capiau S, Lambert WE, Stove CP. Hemato-critical issues in quantitative analysis of dried blood spots: challenges and solutions. Bioanalysis. 2013 Aug;5(16):2023–41.

    Article  PubMed  CAS  Google Scholar 

  56. Wilhelm AJ, den Burger JCG, Swart EL. Therapeutic drug monitoring by dried blood spot: Progress to date and future directions. Clin Pharmacokinet. 2014 Nov;53(11):961–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Clinical Blood Rheology: Volume 1 - 1st Edition - Gordon D.O. Lowe - [Internet]. [cited 2021 Feb 16]. Available from: https://www.routledge.com/Clinical-Blood-Rheology-Volume-1/Lowe/p/book/9780367203733

  58. EMA. Tasigna: EPAR-Product information [Internet]. European Medicines Agency. 2018 [Internet]. 2021. Available from: https://www.ema.europa.eu/en/documents/product-information/tasigna-epar-product-information_en.pdf

  59. Shah VP, Midha KK, Findlay JW, Hill HM, Hulse JD, McGilveray IJ, et al. Bioanalytical method validation--a revisit with a decade of progress. Pharm Res. 2000 Dec;17(12):1551–7.

    Article  CAS  PubMed  Google Scholar 

  60. Rosing H, Man WY, Doyle E, Bult A, Beijnen JH. Bioanalytical liquid chromatographic method validation. A review of current practices and procedures. J Liq Chromatogr Relat Technol. 2000 Jan 18;23(3):329–54.

    Article  CAS  Google Scholar 

  61. Dadgar D, Burnett PE. Issues in evaluation of bioanalytical method selectivity and drug stability. J Pharm Biomed Anal. 1995 Dec;14(1–2):23–31.

    Article  CAS  PubMed  Google Scholar 

  62. Houghton R, Chamberlain J. Conference report: analytical challenges in the qualification and validation of pharmacodynamic biomarkers. Bioanalysis. 2011 May;3(9):945–8.

    Article  CAS  PubMed  Google Scholar 

  63. Matuszewski BK. Standard line slopes as a measure of a relative matrix effect in quantitative HPLC-MS bioanalysis. J Chromatogr B Analyt Technol Biomed Life Sci. 2006 Jan 18;830(2):293–300.

    Article  CAS  PubMed  Google Scholar 

  64. Matuszewski BK, Constanzer ML, Chavez-Eng CM. Strategies for the assessment of matrix effect in quantitative bioanalytical methods based on HPLC−MS/MS. Anal Chem. 2003 Jul 1;75(13):3019–30.

    Article  CAS  PubMed  Google Scholar 

  65. Timmerman P, White S, Cobb Z, de Vries R, Thomas E, van Baar B, et al. Update of the EBF recommendation for the use of DBS in regulated bioanalysis integrating the conclusions from the EBF DBS-microsampling consortium. Bioanalysis. 2013 Sep;5(17):2129–36.

    Article  CAS  PubMed  Google Scholar 

  66. Kretz O, Weiss HM, Schumacher MM, Gross G. In vitro blood distribution and plasma protein binding of the tyrosine kinase inhibitor imatinib and its active metabolite, CGP74588, in rat, mouse, dog, monkey, healthy humans and patients with acute lymphatic leukaemia. Br J Clin Pharmacol. 2004 Aug;58(2):212–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Sparreboom A, van Zuylen L, Brouwer E, Loos WJ, de Bruijn P, Gelderblom H, et al. Cremophor EL-mediated alteration of paclitaxel distribution in human blood: clinical pharmacokinetic implications. Cancer Res. 1999 Apr 1;59(7):1454–7.

    CAS  PubMed  Google Scholar 

  68. Gelderblom H, Verweij J, Nooter K, Sparreboom A. Cremophor EL: the drawbacks and advantages of vehicle selection for drug formulation. Eur J Cancer. 2001 Sep 1;37(13):1590–8.

    Article  CAS  PubMed  Google Scholar 

  69. Loos W. Clinical pharmacokinetics of unbound docetaxel: role of polysorbate 80 and serum proteins. Clinical Pharmacology & Therapeutics. 2003 Oct;74(4):364–71.

    Article  CAS  Google Scholar 

  70. Yu S, Li S, Yang H, Lee F, Wu J-T, Qian MG. A novel liquid chromatography/tandem mass spectrometry based depletion method for measuring red blood cell partitioning of pharmaceutical compounds in drug discovery. Rapid Commun Mass Spectrom. 2005 Jan 30;19(2):250–4.

    Article  CAS  PubMed  Google Scholar 

  71. FDA. Clinical pharmacology and biopharmaceutics review(s) [Internet]. 2008 [cited 2021 Feb 16]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022334s000_ClinPharmR.pdf

  72. van Erp NP, van Herpen CM, de Wit D, Willemsen A, Burger DM, Huitema ADR, et al. A semi-physiological population model to quantify the effect of hematocrit on Everolimus pharmacokinetics and pharmacodynamics in Cancer patients. Clin Pharmacokinet. 2016 Nov;55(11):1447–56.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  73. Verheijen RB, Yu H, Schellens JHM, Beijnen JH, Steeghs N, Huitema ADR. Practical recommendations for therapeutic drug monitoring of kinase inhibitors in oncology. Clinical Pharmacology & Therapeutics. 2017 Nov;102(5):765–76.

    Article  Google Scholar 

  74. Josephs DH, Fisher DS, Spicer J, Flanagan RJ. Clinical pharmacokinetics of tyrosine kinase inhibitors: implications for therapeutic drug monitoring. Ther Drug Monit. 2013;35(5):26.

    Article  CAS  Google Scholar 

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This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.

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Author notes

  1. Valentina Iacuzzi and Bianca Posocco contributed equally to this work.

Authors and Affiliations

  1. Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Via Franco Gallini 2, 33081, Aviano, PN, Italy

    Valentina Iacuzzi, Bianca Posocco, Martina Zanchetta, Sara Gagno, Ariana Soledad Poetto, Michela Guardascione & Giuseppe Toffoli

  2. Department of Chemical and Pharmaceutical Sciences, University of Trieste, Via Licio Giorgieri 1, 34127, Trieste, Italy

    Martina Zanchetta

  3. Doctoral School in Pharmacological Sciences, University of Padova, Lgo Meneghetti 2, 35131, Padova, Italy

    Ariana Soledad Poetto

Authors
  1. Valentina Iacuzzi
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  2. Bianca Posocco
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  4. Sara Gagno
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Contributions

Valentina Iacuzzi: Conceptualization, Investigation, Data curation, Writing - original draft preparation; Bianca Posocco: Conceptualization, Investigation, Data curation, Writing - original draft preparation; Martina Zanchetta: Investigation, Data curation; Sara Gagno: Investigation; Ariana Soledad Poetto: Investigation; Michela Guardascione: Resources; Giuseppe Toffoli: Supervision, Writing – Review & Editing.

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Correspondence to Giuseppe Toffoli.

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Iacuzzi, V., Posocco, B., Zanchetta, M. et al. Dried Blood Spot Technique Applied in Therapeutic Drug Monitoring of Anticancer Drugs: a Review on Conversion Methods to Correlate Plasma and Dried Blood Spot Concentrations. Pharm Res 38, 759–778 (2021). https://doi.org/10.1007/s11095-021-03036-6

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