Point-of-Care Testing of Immunosuppressants in Blood Using Thin-layer Paper Spray Ionization and a Miniature Mass Spectrometer

A new method was proposed for point-of-care testing (POCT) of immunosuppressants in blood using thin-layer paper spray ionization and a miniature mass spectrometer. The aluminum thin-layer plate was used as paper spray substrate, and cut into an equilateral triangle. Aliquots of 10 μL blood sample...

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Main Author: XIE Yi-qing1,2;GUO Xiang-yu1;ZHANG Wen-peng3;OUYANG Zheng3;MA Qiang1
Format: Article
Language:English
Published: Editorial Board of Journal of Chinese Mass Spectrometry Society 2023-11-01
Series:Zhipu Xuebao
Subjects:
Online Access:http://www.jcmss.com.cn/CN/PDF/10.7538/zpxb.2023.0063?token=85ffca2525eb4984aaea3b4a22b60d13
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author XIE Yi-qing1,2;GUO Xiang-yu1;ZHANG Wen-peng3;OUYANG Zheng3;MA Qiang1
author_facet XIE Yi-qing1,2;GUO Xiang-yu1;ZHANG Wen-peng3;OUYANG Zheng3;MA Qiang1
author_sort XIE Yi-qing1,2;GUO Xiang-yu1;ZHANG Wen-peng3;OUYANG Zheng3;MA Qiang1
collection DOAJ
description A new method was proposed for point-of-care testing (POCT) of immunosuppressants in blood using thin-layer paper spray ionization and a miniature mass spectrometer. The aluminum thin-layer plate was used as paper spray substrate, and cut into an equilateral triangle. Aliquots of 10 μL blood sample were loaded on the aluminum thin-layer plate, and then 20 μL methanol was dropped as elution/spray solvent. The tip of the triangular plate was placed 1.0 cm in front of the discontinuous atmospheric pressure interface (DAPI) of the miniature mass spectrometer. When the spray voltage was applied, the sample was eluted from the triangular plate and formed paper spray ionization at the tip. Coupled with the miniature mass spectrometer, five immunosuppressants were detected under negative ion mode. The precursor ions [M-H]- of tacrolimus, sirolimus, everolimus, ciclosporin A, and mycophenolic acid are m/z 802.6, 912.6, 957.1, 1 200.8, 319.1, and product ions are m/z 560.2 and 604.3, m/z 590.3 and 321.2, m/z 590.3 and 365.2, m/z 1 088.8, m/z 287.4 and 275.1, respectively. Based on the observed signal-to-noise ratio (S/N) of the most intense tandem mass spectrometry (MS/MS) fragment peaks and using the S/N=3 and 10 as the criteria, the limits of detection (LODs) and quantitation (LOQs) are estimated to be 0.5-5 mg/L and 1-10 mg/L, respectively. The internal standard method was used for quantitative analysis, and indapamide was used as the internal standard compound. Sufficient linearity for each analyte is obtained with the correlation coefficients (r) greater than 0.99. The proposed method displays good recoveries in the range of 91.0%-114.3% with the relative standard deviations (RSDs) less than 8.4%. Moreover, the developed method was used for the analysis of blood samples, which spiked with tacrolimus, sirolimus, everolimus, cyclosporine A and mycophenolic acid at the concentration of 100 mg/L. The analytical results demonstrated the consistency between the proposed method and the traditional liquid chromatography-mass spectrometry (LC-MS) method. The entire analysis procedure can be completed within 1 min. The proposed method is simple, fast, accurate, efficient, and suitable for POCT of immunosuppressants in blood.
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spelling doaj.art-faa9f8c77761494fa50e42fadbf6ac762024-01-10T05:05:50ZengEditorial Board of Journal of Chinese Mass Spectrometry SocietyZhipu Xuebao1004-29972023-11-0144676276910.7538/zpxb.2023.0063Point-of-Care Testing of Immunosuppressants in Blood Using Thin-layer Paper Spray Ionization and a Miniature Mass SpectrometerXIE Yi-qing1,2;GUO Xiang-yu1;ZHANG Wen-peng3;OUYANG Zheng3;MA Qiang101.Chinese Academy of Inspection and Quarantine, Beijing 100176, China; 2.School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China;3.Department of Precision Instrument, Tsinghua University, Beijing 100084, China A new method was proposed for point-of-care testing (POCT) of immunosuppressants in blood using thin-layer paper spray ionization and a miniature mass spectrometer. The aluminum thin-layer plate was used as paper spray substrate, and cut into an equilateral triangle. Aliquots of 10 μL blood sample were loaded on the aluminum thin-layer plate, and then 20 μL methanol was dropped as elution/spray solvent. The tip of the triangular plate was placed 1.0 cm in front of the discontinuous atmospheric pressure interface (DAPI) of the miniature mass spectrometer. When the spray voltage was applied, the sample was eluted from the triangular plate and formed paper spray ionization at the tip. Coupled with the miniature mass spectrometer, five immunosuppressants were detected under negative ion mode. The precursor ions [M-H]- of tacrolimus, sirolimus, everolimus, ciclosporin A, and mycophenolic acid are m/z 802.6, 912.6, 957.1, 1 200.8, 319.1, and product ions are m/z 560.2 and 604.3, m/z 590.3 and 321.2, m/z 590.3 and 365.2, m/z 1 088.8, m/z 287.4 and 275.1, respectively. Based on the observed signal-to-noise ratio (S/N) of the most intense tandem mass spectrometry (MS/MS) fragment peaks and using the S/N=3 and 10 as the criteria, the limits of detection (LODs) and quantitation (LOQs) are estimated to be 0.5-5 mg/L and 1-10 mg/L, respectively. The internal standard method was used for quantitative analysis, and indapamide was used as the internal standard compound. Sufficient linearity for each analyte is obtained with the correlation coefficients (r) greater than 0.99. The proposed method displays good recoveries in the range of 91.0%-114.3% with the relative standard deviations (RSDs) less than 8.4%. Moreover, the developed method was used for the analysis of blood samples, which spiked with tacrolimus, sirolimus, everolimus, cyclosporine A and mycophenolic acid at the concentration of 100 mg/L. The analytical results demonstrated the consistency between the proposed method and the traditional liquid chromatography-mass spectrometry (LC-MS) method. The entire analysis procedure can be completed within 1 min. The proposed method is simple, fast, accurate, efficient, and suitable for POCT of immunosuppressants in blood.http://www.jcmss.com.cn/CN/PDF/10.7538/zpxb.2023.0063?token=85ffca2525eb4984aaea3b4a22b60d13thin-layer platepaper spray ionizationminiature mass spectrometryimmunosuppressant
spellingShingle XIE Yi-qing1,2;GUO Xiang-yu1;ZHANG Wen-peng3;OUYANG Zheng3;MA Qiang1
Point-of-Care Testing of Immunosuppressants in Blood Using Thin-layer Paper Spray Ionization and a Miniature Mass Spectrometer
Zhipu Xuebao
thin-layer plate
paper spray ionization
miniature mass spectrometry
immunosuppressant
title Point-of-Care Testing of Immunosuppressants in Blood Using Thin-layer Paper Spray Ionization and a Miniature Mass Spectrometer
title_full Point-of-Care Testing of Immunosuppressants in Blood Using Thin-layer Paper Spray Ionization and a Miniature Mass Spectrometer
title_fullStr Point-of-Care Testing of Immunosuppressants in Blood Using Thin-layer Paper Spray Ionization and a Miniature Mass Spectrometer
title_full_unstemmed Point-of-Care Testing of Immunosuppressants in Blood Using Thin-layer Paper Spray Ionization and a Miniature Mass Spectrometer
title_short Point-of-Care Testing of Immunosuppressants in Blood Using Thin-layer Paper Spray Ionization and a Miniature Mass Spectrometer
title_sort point of care testing of immunosuppressants in blood using thin layer paper spray ionization and a miniature mass spectrometer
topic thin-layer plate
paper spray ionization
miniature mass spectrometry
immunosuppressant
url http://www.jcmss.com.cn/CN/PDF/10.7538/zpxb.2023.0063?token=85ffca2525eb4984aaea3b4a22b60d13
work_keys_str_mv AT xieyiqing12guoxiangyu1zhangwenpeng3ouyangzheng3maqiang1 pointofcaretestingofimmunosuppressantsinbloodusingthinlayerpapersprayionizationandaminiaturemassspectrometer