Determination of total and unbound concentrations of lopinavir in plasma using liquid chromatography-tandem mass spectrometry and ultrafiltration methods.
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| Title: | Determination of total and unbound concentrations of lopinavir in plasma using liquid chromatography-tandem mass spectrometry and ultrafiltration methods. |
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| Authors: | Illamola, S. M.1 07silvia@gmail.com, Labat, L.2, Benaboud, S.2,3, Tubiana, R.4,5, Warszawski, J.6,7,8, Tréluyer, J. M.1,2,3,9, Hirt, D.2,3 |
| Source: | Journal of Chromatography B: Analytical Technologies in the Biomedical & Life Sciences. Aug2014, Vol. 965, p216-223. 8p. |
| Subjects: | Lopinavir-ritonavir, Liquid chromatography-mass spectrometry, Therapeutic use of protease inhibitors, Ultrafiltration, Protein binding, Electrospray ionization mass spectrometry, Biological assay |
| Abstract: | Lopinavir is an HIV protease inhibitor with high protein binding (98-99%) in human plasma. This study was designed to develop an ultrafiltration method to measure the unbound concentrations of lopinavir overcoming the non-specific binding issue. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of total concentrations of lopinavir in plasma was developed and validated, and an adaptation was also optimized and validated for the determination of unbound concentrations. The chromatographic separation was performed with a C18 column (100mm×2.1mm i.d., 5µm particle size) using a mobile phase containing deionized water with formic acid, and acetonitrile, with gradient elution at a flow-rate of 350µLmin-1. Identification of the compounds was performed by multiple reaction monitoring, using electrospray ionization in positive ion mode. The method was validated over a clinical range of 0.01-1µg/mL for human plasma ultrafiltrate and 0.1-15µg/mL in human plasma. The inter and intra-assay accuracies and precisions were between 0.23% and 11.37% for total lopinavir concentrations, and between 3.50% and 13.30% for plasma ultrafiltrate (unbound concentration). The ultrafiltration method described allows an accurate separation of the unbound fraction of lopinavir, circumscribing the loss of drug by nonspecific binding (NSB), and the validated LC-MS/MS methodology proposed is suitable for the determination of total and unbound concentrations of lopinavir in clinical practice. [ABSTRACT FROM AUTHOR] |
| Copyright of Journal of Chromatography B: Analytical Technologies in the Biomedical & Life Sciences is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Engineering Source |
| FullText | Text: Availability: 0 |
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| Header | DbId: egs DbLabel: Engineering Source An: 97335306 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: Determination of total and unbound concentrations of lopinavir in plasma using liquid chromatography-tandem mass spectrometry and ultrafiltration methods. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Illamola%2C+S%2E+M%2E%22">Illamola, S. M.</searchLink><relatesTo>1</relatesTo><i> 07silvia@gmail.com</i><br /><searchLink fieldCode="AR" term="%22Labat%2C+L%2E%22">Labat, L.</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Benaboud%2C+S%2E%22">Benaboud, S.</searchLink><relatesTo>2,3</relatesTo><br /><searchLink fieldCode="AR" term="%22Tubiana%2C+R%2E%22">Tubiana, R.</searchLink><relatesTo>4,5</relatesTo><br /><searchLink fieldCode="AR" term="%22Warszawski%2C+J%2E%22">Warszawski, J.</searchLink><relatesTo>6,7,8</relatesTo><br /><searchLink fieldCode="AR" term="%22Tréluyer%2C+J%2E+M%2E%22">Tréluyer, J. M.</searchLink><relatesTo>1,2,3,9</relatesTo><br /><searchLink fieldCode="AR" term="%22Hirt%2C+D%2E%22">Hirt, D.</searchLink><relatesTo>2,3</relatesTo> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Journal+of+Chromatography+B%3A+Analytical+Technologies+in+the+Biomedical+%26+Life+Sciences%22">Journal of Chromatography B: Analytical Technologies in the Biomedical & Life Sciences</searchLink>. Aug2014, Vol. 965, p216-223. 8p. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Lopinavir-ritonavir%22">Lopinavir-ritonavir</searchLink><br /><searchLink fieldCode="DE" term="%22Liquid+chromatography-mass+spectrometry%22">Liquid chromatography-mass spectrometry</searchLink><br /><searchLink fieldCode="DE" term="%22Therapeutic+use+of+protease+inhibitors%22">Therapeutic use of protease inhibitors</searchLink><br /><searchLink fieldCode="DE" term="%22Ultrafiltration%22">Ultrafiltration</searchLink><br /><searchLink fieldCode="DE" term="%22Protein+binding%22">Protein binding</searchLink><br /><searchLink fieldCode="DE" term="%22Electrospray+ionization+mass+spectrometry%22">Electrospray ionization mass spectrometry</searchLink><br /><searchLink fieldCode="DE" term="%22Biological+assay%22">Biological assay</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Lopinavir is an HIV protease inhibitor with high protein binding (98-99%) in human plasma. This study was designed to develop an ultrafiltration method to measure the unbound concentrations of lopinavir overcoming the non-specific binding issue. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of total concentrations of lopinavir in plasma was developed and validated, and an adaptation was also optimized and validated for the determination of unbound concentrations. The chromatographic separation was performed with a C18 column (100mm×2.1mm i.d., 5µm particle size) using a mobile phase containing deionized water with formic acid, and acetonitrile, with gradient elution at a flow-rate of 350µLmin-1. Identification of the compounds was performed by multiple reaction monitoring, using electrospray ionization in positive ion mode. The method was validated over a clinical range of 0.01-1µg/mL for human plasma ultrafiltrate and 0.1-15µg/mL in human plasma. The inter and intra-assay accuracies and precisions were between 0.23% and 11.37% for total lopinavir concentrations, and between 3.50% and 13.30% for plasma ultrafiltrate (unbound concentration). The ultrafiltration method described allows an accurate separation of the unbound fraction of lopinavir, circumscribing the loss of drug by nonspecific binding (NSB), and the validated LC-MS/MS methodology proposed is suitable for the determination of total and unbound concentrations of lopinavir in clinical practice. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Journal of Chromatography B: Analytical Technologies in the Biomedical & Life Sciences is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1016/j.jchromb.2014.06.034 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 8 StartPage: 216 Subjects: – SubjectFull: Lopinavir-ritonavir Type: general – SubjectFull: Liquid chromatography-mass spectrometry Type: general – SubjectFull: Therapeutic use of protease inhibitors Type: general – SubjectFull: Ultrafiltration Type: general – SubjectFull: Protein binding Type: general – SubjectFull: Electrospray ionization mass spectrometry Type: general – SubjectFull: Biological assay Type: general Titles: – TitleFull: Determination of total and unbound concentrations of lopinavir in plasma using liquid chromatography-tandem mass spectrometry and ultrafiltration methods. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Illamola, S. M. – PersonEntity: Name: NameFull: Labat, L. – PersonEntity: Name: NameFull: Benaboud, S. – PersonEntity: Name: NameFull: Tubiana, R. – PersonEntity: Name: NameFull: Warszawski, J. – PersonEntity: Name: NameFull: Tréluyer, J. M. – PersonEntity: Name: NameFull: Hirt, D. IsPartOfRelationships: – BibEntity: Dates: – D: 15 M: 08 Text: Aug2014 Type: published Y: 2014 Identifiers: – Type: issn-print Value: 15700232 Numbering: – Type: volume Value: 965 Titles: – TitleFull: Journal of Chromatography B: Analytical Technologies in the Biomedical & Life Sciences Type: main |
| ResultId | 1 |
