Abstract
The Jatropha curcas plant (Jatropha) has been proposed as a source of biodiesel fuel, as it yields crude glycerol as an abundant by-product. Its by-products could serve as a starting material in making glycerol for FDA-regulated products. Jatropha is not regarded as a source of edible vegetable oil since it contains phorbol esters (PEs). PEs, even at very low exposure concentrations, demonstrate various toxicities in humans and animals, but may not be detected by routine impurity analyses. Here, we demonstrate the development of a rapid and simplified method for the detection and quantification of Jatropha-derived PE toxins using ambient ionization mass spectrometry. To do this, we successfully coupled a paper spray ambient ionization source with an ion trap portable mass spectrometer. The paper spray source was assembled using chromatography papers, and analyte ions were generated by applying a high voltage to a wetted paper triangle loaded with PE standards. For method development, we used commercially available PE standards on an ion trap portable mass spectrometer. Standard solutions were prepared using ethanol with PE concentrations ranging from 1.0 to 0.0001 mg mL−1. Spike and recovery experiments were performed using USP grade and commercially available glycerol. To discern chemical differences between samples, we applied multivariate data analysis. Based on the results obtained, paper spray coupled with a portable mass spectrometric method can be successfully adopted for the analysis of toxic contaminants present in glycerol-based consumer products with LOD and LOQ of 0.175 μg mL−1 and 0.3 μg mL−1 respectively. This direct, simple design, and low-cost sampling and ionization method enables fast screening with high sensitivity in non-laboratory settings.
Similar content being viewed by others
References
Sommers CD, Keire DA. Detection of possible economically motivated adulterants in heparin sodium and low molecular weight heparins with a colorimetric microplate based assay. Anal Chem. 2011;83(18):7102–8.
Scholl PF, Bergana MM, Yakes BJ, Xie Z, Zbylut S, Downey G, et al. Effects of the adulteration technique on the near-infrared detection of melamine in milk powder. J Agric Food Chem. 2017;65(28):5799–809.
Ren Y, Wang H, Liu JJ, Zhang ZP, McLuckey MN, Ouyang Z. Analysis of biological samples using paper spray mass spectrometry: an investigation of impacts by the substrates, solvents and elution methods. Chromatographia. 2013;76(19–20):1339–46.
Roux PP, Ballif BA, Anjum R, Gygi SP, Blenis J. Tumor-promoting phorbol esters and activated Ras inactivate the tuberous sclerosis tumor suppressor complex via p90 ribosomal S6 kinase. Proc Natl Acad Sci U S A. 2004;101(37):13489–94.
Baird WM, Boutwell RK. Tumor-promoting activity of phorbol and four diesters of phorbol in mouse skin. Cancer Res. 1971;31(8):1074–9.
Bandomir J, Kaule S, Schmitz KP, Sternberg K, Petersen S, Kragl U. Usage of different vessel models in a flow-through cell: in vitro study of a novel coated balloon catheter. RSC Adv. 2015;5(15):11604–10.
Sarode K, Spelber DA, Bhatt DL, Mohammad A, Prasad A, Brilakis ES, et al. Drug delivering technology for endovascular management of infrainguinal peripheral artery disease. JACC Cardiovasc Interv. 2014;7(8):827–39.
Balaji Viswanathan RS, Kapila S, Lorbert S. Characterization and quantification of phorbol esters by tandem ESI-FT-ICR-MS. LC GC Chromatographyonlinecom. 2012;10(2):16–25.
Baldini M, Ferfuia C, Bortolomeazzi R, Verardo G, Pascali J, Piasentier E, et al. Determination of phorbol esters in seeds and leaves of Jatropha curcas and in animal tissue by high-performance liquid chromatography tandem mass spectrometry. Ind Crop Prod. 2014;59:268–76.
Nishshanka U, Jayasuriya H, Chattopadhaya C, Kijak PJ, Chu P-S, Reimschuessel R, et al. Screening for toxic phorbol esters in jerky pet treat products using LC–MS. J Chromatogr B. 2016;1020:90–5.
Herath K, Girard L, Reimschuessel R, Jayasuriya H. Application of time-of-flight mass spectrometry for screening of crude glycerins for toxic phorbol ester contaminants. J Chromatogr B. 2017;1046:226–34.
Cooks RG, Ouyang Z, Takats Z, Wiseman JM. Ambient mass spectrometry. Science. 2006;311(5767):1566–70.
Harris GA, Galhena AS, Fernandez FM. Ambient sampling/ionization mass spectrometry: applications and current trends. Anal Chem. 2011;83(12):4508–38.
Liu JJ, Wang H, Manicke NE, Lin JM, Cooks RG, Ouyang Z. Development, characterization, and application of paper spray ionization. Anal Chem. 2010;82(6):2463–71.
Wang H, Liu JJ, Cooks RG, Ouyang Z. Paper spray for direct analysis of complex mixtures using mass spectrometry. Angew Chem Int Ed. 2010;49(5):877–80.
Michely JA, Meyer MR, Maurer HH. Paper spray ionization coupled to high resolution tandem mass spectrometry for comprehensive urine drug testing in comparison to liquid chromatography-coupled techniques after urine precipitation or dried urine spot workup. Anal Chem. 2017;89(21):11779–86.
Wang H, Manicke NE, Yang Q, Zheng L, Shi R, Cooks RG, et al. Direct analysis of biological tissue by paper spray mass spectrometry. Anal Chem. 2011;83(4):1197–201.
Brown H, Oktem B, Windom A, Doroshenko V, Evans-Nguyen K. Direct analysis in real time (DART) and a portable mass spectrometer for rapid identification of common and designer drugs on-site. Forensic Chem. 2016;1:66–73.
Hua W, Hu H, Chen F, Tang L, Peng T, Wang Z. Rapid isolation and purification of phorbol esters from Jatropha curcas by high-speed countercurrent chromatography. J Agric Food Chem. 2015;63(10):2767–72.
Roach JS, Devappa RK, Makkar HPS, Becker K. Isolation, stability and bioactivity of Jatropha curcas phorbol esters. Fitoterapia. 2012;83(3):586–92.
Wang ZG, Tang L, Hu HL, Guo YR, Peng T, Yan F, et al. Metabolic profiling assisted quality control of phorbol esters in Jatropha curcas seed by high-performance liquid chromatography using a fused-core column. J Agric Food Chem. 2012;60(38):9567–72.
Yang Q, Wang H, Maas JD, Chappell WJ, Manicke NE, Cooks RG, et al. Paper spray ionization devices for direct, biomedical analysis using mass spectrometry. Int J Mass Spectrom. 2012;312:201–7.
Manicke NE, Yang Q, Wang H, Oradu S, Ouyang Z, Cooks RG. Assessment of paper spray ionization for quantitation of pharmaceuticals in blood spots. Int J Mass Spectrom. 2011;300(2):123–9.
Espy RD, Muliadi AR, Ouyang Z, Cooks RG. Spray mechanism in paper spray ionization. Int J Mass Spectrom. 2012;325-327:167–71.
Manicke NE, Bills BJ, Zhang C. Analysis of biofluids by paper spray MS: advances and challenges. Bioanalysis. 2016;8(6):589–606.
Blain MG, Riter LS, Cruz D, Austin DE, Wu G, Plass WR, et al. Towards the hand-held mass spectrometer: design considerations, simulation, and fabrication of micrometer-scaled cylindrical ion traps. Int J Mass Spectrom. 2004;236(1):91–104.
Rice JM, Dudek GO, Barber M. Mass spectra of nucleic acid derivatives. Pyrimidines J Am Chem Soc. 1965;87(20).
Nothias-Scaglia LF, Schmitz-Afonso I, Renucci F, Roussi F, Touboul D, Costa J, et al. Insights on profiling of phorbol, deoxyphorbol, ingenol and jatrophane diterpene esters by high performance liquid chromatography coupled to multiple stage mass spectrometry. J Chromatogr A. 2015;1422:128–39.
Kongmany S, Hoa TT, Hanh LTN, Imamura K, Maeda Y, Boi LV. Semi-preparative HPLC separation followed by HPLC/UV and tandem mass spectrometric analysis of phorbol esters in Jatropha seed. J Chromatogr B. 2016;1038:63–72.
Vogg G, Achatz S, Kettrup A, Sandermann H. Fast, sensitive and selective liquid chromatographic-tandem mass spectrometric determination of tumor-promoting diterpene eaters. J Chromatogr A. 1999;855(2):563–73.
Valliyappan T, Bakhshi NN, Dalai AK. Pyrolysis of glycerol for the production of hydrogen or syn gas. Bioresour Technol. 2008;99(10):4476–83.
Xia J, Wishart DS. Using MetaboAnalyst 3.0 for comprehensive metabolomics data analysis. Curr Protoc Bioinformatics: Wiley; 2016.
Xia JG, Sinelnikov IV, Han B, Wishart DS. MetaboAnalyst 3.0-making metabolomics more meaningful. Nucleic Acids Res. 2015;43(W1):W251–W7.
Acknowledgements
This project was supported in part by an appointment to the Research Participation Program at the Center for Devices and Radiological Health, administrated by the Oak Ridge Institute for Science and Education through an inter-agency agreement between US Department of Energy and the US Food and Drug Administration (FDA). Additionally, we would like to thank Dr. Steven Wolfgang from the FDA, Center for Drug Evaluation and Research, for his valuable guidance on the project, as well as Dr. Jose Centeno and Dr. Benita J. Dair, for their management support.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that there are no conflicts of interest.
Disclaimer
The findings and conclusions in this paper have not been formally disseminated by the FDA and should not be construed to represent any agency determination or policy. The mention of commercial products, their sources, or their use regarding material reported herein is not to be construed as either actual or implied endorsement of such products by the US Department of Health and Human Services.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
ESM 1
(PDF 527 kb)
Rights and permissions
About this article
Cite this article
Wickramasekara, S., Kaushal, R., Li, H. et al. Paper spray portable mass spectrometry for screening of phorbol ester contamination in glycerol-based medical products. Anal Bioanal Chem 411, 2707–2714 (2019). https://doi.org/10.1007/s00216-019-01717-1
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00216-019-01717-1