title: Ultra-performance liquid chromatography tandem mass spectrometry for determination of Direct Acting Antiviral drugs in human liver fine needle aspirates.
abstract: An ultra-performance liquid chromatography with triple quadrupole mass spectrometry method was developed and validated for the determination of direct acting antiviral drug concentrations in human liver fine needle aspirates. Liver fine needle aspirate (FNA) biopsy samples were homogenized in acetonitrile to stabilize the analytes and precipitate protein. The acetonitrile supernatants were diluted with internal standards and mobile phase. Separation was achieved with a Waters Acquity BEH C18 column (50×2.1mm, 1.7um) with a gradient elution of 0.1% formic acid in water and acetonitrile. The total run time was 4.25min. Detection of analytes was achieved using electrospray ionization (positive mode) and triple quadrupole selected reaction monitoring. Standard curve concentrations ranged from 12.5 to 5000ng/mL for dasabuvir and the m1 metabolite of dasabuvir, 1.25 to 2500ng/mL for ombitasvir and ritonavir, and 5.00 to 5000ng/mL for paritaprevir. The intra- and inter-day accuracy and precision were less than 13.7% in low, medium, and high quality control samples. The validated method was applied to the analysis of a liver fine needle aspirate of a patient undergoing direct acting antiviral therapy for hepatitis C virus.
authors.affiliation: Translational Pharmacology Research Core, Department of Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, New York State Center of Excellence in Bioinformatics and Life Sciences, University at Buffalo, Buffalo, NY, USA. Electronic address: ocque@buffalo.edu.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Ocque
authors.affiliation: Translational Pharmacology Research Core, Department of Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, New York State Center of Excellence in Bioinformatics and Life Sciences, University at Buffalo, Buffalo, NY, USA.
authors.forename: Colleen E
authors.initials: CE
authors.lastname: Hagler
authors.affiliation: Translational Pharmacology Research Core, Department of Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, New York State Center of Excellence in Bioinformatics and Life Sciences, University at Buffalo, Buffalo, NY, USA.
authors.forename: Robin
authors.initials: R
authors.lastname: DiFrancesco
authors.affiliation: Translational Pharmacology Research Core, Department of Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, New York State Center of Excellence in Bioinformatics and Life Sciences, University at Buffalo, Buffalo, NY, USA.
authors.forename: Gene D
authors.initials: GD
authors.lastname: Morse
authors.affiliation: Division of Gastroenterology and Hepatology and Center for Clinical and Research in Liver Disease, Jacobs School of Medicine, University at Buffalo, Buffalo, NY, USA.
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Talal
mesh_terms: D015081:2-Naphthylamine; D000813:Anilides / Q000032:analysis*; D000818:Animals; D000998:Antiviral Agents / Q000032:analysis*; D002219:Carbamates / Q000032:analysis*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003521:Cyclopropanes; D006801:Humans; D047029:Lactams, Macrocyclic; D057230:Limit of Detection; D008099:Liver / Q000737:chemistry*; D047028:Macrocyclic Compounds / Q000032:analysis*; D009339:Needles; D011392:Proline / Q000031:analogs & derivatives; D015203:Reproducibility of Results; D013449:Sulfonamides / Q000032:analysis*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014498:Uracil / Q000031:analogs & derivatives* / Q000032:analysis; D014633:Valine
chemical_list: D000813:Anilides; D000998:Antiviral Agents; D002219:Carbamates; D003521:Cyclopropanes; D047029:Lactams, Macrocyclic; D047028:Macrocyclic Compounds; D013449:Sulfonamides; C586094:ombitasvir; D014498:Uracil; D011392:Proline; D015081:2-Naphthylamine; C588260:dasabuvir; D014633:Valine; C585405:paritaprevir
keywords: Dasabuvir; Fine needle aspirate; Liver; Ombitasvir; Paritaprevir; UPLC–MS/MS