Enhancement of human plasma glucosylceramide assay sensitivity using delipidized plasma
Glucosylceramide (GL-1) level in human has been considered as a surrogate biomarker for enzyme replacement and substrate reduction therapies (ERT and SRT) for Gaucher and Fabry patients. Due to the high endogenous level of GL-1 in human plasma, it is difficult to achieve the analytical sensitivity o...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2016-09-01
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| Series: | Molecular Genetics and Metabolism Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2214426916300520 |
| _version_ | 1818618586404487168 |
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| author | Kefei Zheng Allena Ji Lee Lee Chung Kerry Culm-Merdek Hanlan Liu Susan Richards Crystal Sung |
| author_facet | Kefei Zheng Allena Ji Lee Lee Chung Kerry Culm-Merdek Hanlan Liu Susan Richards Crystal Sung |
| author_sort | Kefei Zheng |
| collection | DOAJ |
| description | Glucosylceramide (GL-1) level in human has been considered as a surrogate biomarker for enzyme replacement and substrate reduction therapies (ERT and SRT) for Gaucher and Fabry patients. Due to the high endogenous level of GL-1 in human plasma, it is difficult to achieve the analytical sensitivity of plasma GL-1 below the normal endogenous level (1.7 μg/mL to 6.6 μg/mL) when using the standard addition method and regular plasma matrix for standard curve. A high sensitivity plasma GL-1 assay with LLOQ at 0.1 μg/mL was developed and validated using delipidized plasma so that patient plasma concentrations that are below normal reference range can be measured accurately. The normal reference range was established from 120 healthy donors using this developed new method. Twenty-three Fabry patient plasma samples including baseline and post-investigation drug treatment samples were measured. All post-treatment samples showed GL-1 concentration below 2.0 μg/mL, indicating the utility of the reported high sensitivity assay using delipidized plasma for monitoring the plasma GL-1 biomarker level in patients. |
| first_indexed | 2024-12-16T17:23:57Z |
| format | Article |
| id | doaj.art-d9151cf14319471e97da8f61841a78e4 |
| institution | Directory Open Access Journal |
| issn | 2214-4269 |
| language | English |
| last_indexed | 2024-12-16T17:23:57Z |
| publishDate | 2016-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Genetics and Metabolism Reports |
| spelling | doaj.art-d9151cf14319471e97da8f61841a78e42022-12-21T22:23:07ZengElsevierMolecular Genetics and Metabolism Reports2214-42692016-09-018C777910.1016/j.ymgmr.2016.07.004Enhancement of human plasma glucosylceramide assay sensitivity using delipidized plasmaKefei ZhengAllena JiLee Lee ChungKerry Culm-MerdekHanlan LiuSusan RichardsCrystal SungGlucosylceramide (GL-1) level in human has been considered as a surrogate biomarker for enzyme replacement and substrate reduction therapies (ERT and SRT) for Gaucher and Fabry patients. Due to the high endogenous level of GL-1 in human plasma, it is difficult to achieve the analytical sensitivity of plasma GL-1 below the normal endogenous level (1.7 μg/mL to 6.6 μg/mL) when using the standard addition method and regular plasma matrix for standard curve. A high sensitivity plasma GL-1 assay with LLOQ at 0.1 μg/mL was developed and validated using delipidized plasma so that patient plasma concentrations that are below normal reference range can be measured accurately. The normal reference range was established from 120 healthy donors using this developed new method. Twenty-three Fabry patient plasma samples including baseline and post-investigation drug treatment samples were measured. All post-treatment samples showed GL-1 concentration below 2.0 μg/mL, indicating the utility of the reported high sensitivity assay using delipidized plasma for monitoring the plasma GL-1 biomarker level in patients.http://www.sciencedirect.com/science/article/pii/S2214426916300520GlucosylceramideGlobotriaosylceramideLiquid chromatography–tandem mass spectrometry (LC/MS/MS)Delipidized plasmaSensitivityStandard addition method |
| spellingShingle | Kefei Zheng Allena Ji Lee Lee Chung Kerry Culm-Merdek Hanlan Liu Susan Richards Crystal Sung Enhancement of human plasma glucosylceramide assay sensitivity using delipidized plasma Molecular Genetics and Metabolism Reports Glucosylceramide Globotriaosylceramide Liquid chromatography–tandem mass spectrometry (LC/MS/MS) Delipidized plasma Sensitivity Standard addition method |
| title | Enhancement of human plasma glucosylceramide assay sensitivity using delipidized plasma |
| title_full | Enhancement of human plasma glucosylceramide assay sensitivity using delipidized plasma |
| title_fullStr | Enhancement of human plasma glucosylceramide assay sensitivity using delipidized plasma |
| title_full_unstemmed | Enhancement of human plasma glucosylceramide assay sensitivity using delipidized plasma |
| title_short | Enhancement of human plasma glucosylceramide assay sensitivity using delipidized plasma |
| title_sort | enhancement of human plasma glucosylceramide assay sensitivity using delipidized plasma |
| topic | Glucosylceramide Globotriaosylceramide Liquid chromatography–tandem mass spectrometry (LC/MS/MS) Delipidized plasma Sensitivity Standard addition method |
| url | http://www.sciencedirect.com/science/article/pii/S2214426916300520 |
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