Study of Sirolimus Adsorption and Preparation of Its Samples in Methanol, Acetonitrile and Their Mixtures with Water for HPLC–MS/MS Analysis

  • Artem D. RogachevEmail author
  • Dmitry V. Trebushat
  • Andrey N. Kudryashov
  • Andrey G. Pokrovsky
Short Communication


The paper discusses some of the problems associated with the preparation and reversed-phase HPLC analysis of sirolimus samples in mixtures of water with methanol or acetonitrile with different content of the latter. It was shown that when the sirolimus samples were evaporated to dryness in polypropylene tubes, almost quantitative irreversible adsorption of the substance occurred. The loss of sirolimus can be avoided by using glass tubes for sample preparation when a complete removal of a solvent is necessary. Preparation of sirolimus samples in water–methanol or water-acetonitrile mixtures can lead to a gradual adsorption of the substance on the walls of a glass vial in case of a low organic solvent content. It was shown that a reconstitution solution containing about 50% of an organic solvent should be used to analyze sirolimus by the RP-HPLC method, since the analysis of samples dissolved in pure acetonitrile or methanol is limited by the amount of sample injected due to broadening or distortion of the chromatographic peak.


High-performance liquid chromatography Sirolimus Sample preparation 



The research was supported in part by the Ministry of Science and Higher Education of Russia (task N 17.5484.2017/BY). The authors are grateful to Dr. Sergey V. Cheresiz for help in preparation of the manuscript.

Compliance with Ethical Standards

Conflict of Interest

The authors declare no conflict of interest.

Ethical Approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Supplementary material

10337_2019_3835_MOESM1_ESM.docx (25 kb)
Supplementary material 1 (DOCX 24 kb)


  1. 1.
    Di Lorenzo E, Sauro R, Capasso M, Lanni F, Lanzillo T, Carbone G, Manganelli F, Palmieri V, Serino V, Pagliuca MR, Rosato G, Suryapranata H, De Luca G (2016) Long-term results of the randomized comparison of everolimus-eluting stents and sirolimus-eluting stent in patients with ST elevation myocardial infarction (RACES-MI trial). Int J Cardiol 202:177–182CrossRefGoogle Scholar
  2. 2.
    Siller-Matula JM, Tentzeris I, Vogel B, Schacherl S, Jarai R, Geppert A, Unger G, Huber K (2010) Tacrolimus-eluting carbon-coated stents versus sirolimus-eluting stents for prevention of symptom-driven clinical end points. Clin Res Cardiol 99(10):645–650CrossRefGoogle Scholar
  3. 3.
    Iqbal J, Serruys PW, Silber S, Kelbaek H, Richardt G, Morel MA, Negoita M, Buszman PE, Windecker S (2015) Comparison of zotarolimus- and everolimus-eluting coronary stents: final 5-year report of the RESOLUTE all-comers trial. Circ Cardiovasc Interv 8(6):e002230PubMedGoogle Scholar
  4. 4.
    Navarrete A, Martínez-Alcázar MP, Durán I, Calvo E, Valenzuela B, Barbas C, García A (2013) Simultaneous online SPE-HPLC-MS/MS analysis of docetaxel, temsirolimus and sirolimus in whole blood and human plasma. J Chromatogr B 921–922:35–42CrossRefGoogle Scholar
  5. 5.
    Tszyrsznic W, Borowiec A, Pawlowska E, Jazwiec R, Zochowska D, Bartlomiejczyk I, Zegarska J, Paczek L, Dadlez M (2013) Two rapid ultra performance liquid chromatography/tandem mass spectrometry (UPLC/MS/MS) methods with common sample pretreatment for therapeutic drug monitoring of immunosuppressants compared to immunoassay. J Chromatogr B 928:9–15CrossRefGoogle Scholar
  6. 6.
    Constantinescu I, Istrate G (2013) Quantification of cyclosporine, tacrolimus and sirolimus concentrations from whole blood of bone marrow and renal transplantated patients-benefits for long term outcome and survival. Rev Chim (Bucharest, Rom.) 64:1365–1371Google Scholar
  7. 7.
    Zhang X, Louie A, Li X, Shi R, Kelley RK, Huang Y (2012) A simple and sensitive LC–MS/MS method for simultaneous determination of temsirolimus and its major metabolite in human whole blood. Chromatographia 75:1405–1413CrossRefGoogle Scholar
  8. 8.
    Rigo-Bonnin R, Arbiol-Roca A, de Aledo-Castillo JMG, Alía P (2015) Simultaneous measurement of cyclosporine a, everolimus, sirolimus and tacrolimus concentrations in human blood by UPLC–MS/MS. Chromatographia 78:1459–1474CrossRefGoogle Scholar
  9. 9.
    Rajender G, Narayanan NG (2010) Liquid chromatography-tandem mass spectrometry method for determination of Sirolimus coated drug eluting nano porous carbon stents. Biomed Chromatogr 24:329–334PubMedGoogle Scholar
  10. 10.
    Molnár PM, Dux L, Reinauer H, Kress M, Akerboom T, Szederkényi E, Kaiser P (2011) Procedure for determination of immunosuppressive drugs in whole blood with liquid chromatography-isotope dilution mass spectrometry. Clin Lab 57:983–992PubMedGoogle Scholar
  11. 11.
    Bodnar-Broniarczyk M, Pawiński T, Kunicki PK (2019) Isotope-labeled versus analog internal standard in LC-MS/MS method for tacrolimus determination in human whole blood samples—a compensation of matrix effects. J Chromatogr B 1104:220–227CrossRefGoogle Scholar
  12. 12.
    Chico DE, Given RL, Miller BT (2003) Binding of cationic cell-permeable peptides to plastic and glass. Peptides 24:3–9CrossRefGoogle Scholar
  13. 13.
    Kristensen K, Henriksen JR, Andresen TL (2015) Adsorption of cationic peptides to solid surfaces of glass and plastic. PLoS One 10(5):e0122419CrossRefGoogle Scholar
  14. 14.
    Duncan MR, Lee JM, Warchol MP (1995) Influence of surfactants upon protein/peptide adsorption to glass and polypropylene. Int J Pharm 120:179–188CrossRefGoogle Scholar
  15. 15.

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.N. N. Vorozhtsov Novosibirsk Institute of Organic ChemistrySiberian Branch of Russian Academy of SciencesNovosibirskRussia
  2. 2.Novosibirsk State UniversityNovosibirskRussia
  3. 3.Angioline Interventional DeviceNovosibirskRussia

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