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Determination of total and unbound concentrations of lopinavir in plasma using liquid chromatography-tandem mass spectrometry and ultrafiltration methods.
J Chromatogr B Analyt Technol Biomed Life Sci. 2014 Aug 15; 965:216-23.JC

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 (100 mm × 2.1mm i.d., 5 μm particle size) using a mobile phase containing deionized water with formic acid, and acetonitrile, with gradient elution at a flow-rate of 350 μL min(-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 0.01-1 μg/mL for human plasma ultrafiltrate and 0.1-15 μg/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.

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Authors+Show Affiliations

Illamola SM
Unité de Recherche Clinique, AP-HP, Hôpital Tarnier, Paris, France. Electronic address: 07silvia@gmail.com.
Labat L
Service de Pharmacologie Clinique, AP-HP, Groupe Hospitalier Paris Centre, Paris, France.
Benaboud S
Service de Pharmacologie Clinique, AP-HP, Groupe Hospitalier Paris Centre, Paris, France; EAU08 Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
Tubiana R
AP-HP, Hôpital Pitié Salpêtrière, Service de maladies infectieuses, Paris, France; Sorbonne université, UPMC Paris 06, UMR_S 1136 Pierre Louis Institute of Epidemiology and Public Health, F-75013, Paris, France.
Warszawski J
INSERM, Centre for research in Epidemiology and Population Health, U1018, Equipe VIH et IST, Le Kremlin Bicêtre, France; AP-HP, Hôpital Bicêtre, Service d'Epidemiologie et Santé Publique, Le Kremlin-Bicêtre, France; Université Paris Sud, UMRS 1018, Le Kremlin-Bicêtre, France.
Tréluyer JM
Unité de Recherche Clinique, AP-HP, Hôpital Tarnier, Paris, France; Service de Pharmacologie Clinique, AP-HP, Groupe Hospitalier Paris Centre, Paris, France; EAU08 Université Paris Descartes, Sorbonne Paris Cité, Paris, France; CIC-0901 INSERM, Cochin-Necker, Paris, France.
Hirt D
Service de Pharmacologie Clinique, AP-HP, Groupe Hospitalier Paris Centre, Paris, France; EAU08 Université Paris Descartes, Sorbonne Paris Cité, Paris, France.

MeSH

Chromatography, High Pressure LiquidClinical Trials, Phase II as TopicClinical Trials, Phase III as TopicFemaleHIV InfectionsHumansInfectious Disease Transmission, VerticalLopinavirPregnancyPregnancy Complications, InfectiousRandomized Controlled Trials as TopicReproducibility of ResultsSensitivity and SpecificityTandem Mass SpectrometryUltrafiltration

Pub Type(s)

Journal Article

Language

eng

PubMed ID

25049210

Citation

Illamola, S M., et al. "Determination of Total and Unbound Concentrations of Lopinavir in Plasma Using Liquid Chromatography-tandem Mass Spectrometry and Ultrafiltration Methods." Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences, vol. 965, 2014, pp. 216-23.
Illamola SM, Labat L, Benaboud S, et al. Determination of total and unbound concentrations of lopinavir in plasma using liquid chromatography-tandem mass spectrometry and ultrafiltration methods. J Chromatogr B Analyt Technol Biomed Life Sci. 2014;965:216-23.
Illamola, S. M., Labat, L., Benaboud, S., Tubiana, R., Warszawski, J., Tréluyer, J. M., & Hirt, D. (2014). Determination of total and unbound concentrations of lopinavir in plasma using liquid chromatography-tandem mass spectrometry and ultrafiltration methods. Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences, 965, 216-23. https://doi.org/10.1016/j.jchromb.2014.06.034
Illamola SM, et al. Determination of Total and Unbound Concentrations of Lopinavir in Plasma Using Liquid Chromatography-tandem Mass Spectrometry and Ultrafiltration Methods. J Chromatogr B Analyt Technol Biomed Life Sci. 2014 Aug 15;965:216-23. PubMed PMID: 25049210.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Determination of total and unbound concentrations of lopinavir in plasma using liquid chromatography-tandem mass spectrometry and ultrafiltration methods. AU - Illamola,S M, AU - Labat,L, AU - Benaboud,S, AU - Tubiana,R, AU - Warszawski,J, AU - Tréluyer,J M, AU - Hirt,D, Y1 - 2014/07/08/ PY - 2014/03/10/received PY - 2014/06/27/revised PY - 2014/06/29/accepted PY - 2014/7/23/entrez PY - 2014/7/23/pubmed PY - 2015/3/31/medline KW - Lopinavir KW - Nonspecific binding KW - UPLC–MS/MS KW - Ultrafiltration KW - Unbound fraction SP - 216 EP - 23 JF - Journal of chromatography. B, Analytical technologies in the biomedical and life sciences JO - J Chromatogr B Analyt Technol Biomed Life Sci VL - 965 N2 - 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 (100 mm × 2.1mm i.d., 5 μm particle size) using a mobile phase containing deionized water with formic acid, and acetonitrile, with gradient elution at a flow-rate of 350 μL min(-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 0.01-1 μg/mL for human plasma ultrafiltrate and 0.1-15 μg/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. SN - 1873-376X UR - https://www.unboundmedicine.com/medline/citation/25049210/Determination_of_total_and_unbound_concentrations_of_lopinavir_in_plasma_using_liquid_chromatography_tandem_mass_spectrometry_and_ultrafiltration_methods_ DB - PRIME DP - Unbound Medicine ER -
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