Development and validation of a UPLC-MS/MS method for the simultaneous determination of paritaprevir and ritonavir in rat liver.
OBJECTIVE
Determination of paritaprevir and ritonavir in rat liver tissue samples.


RESULTS
We successfully validated a UPLC-MS/MS method to measure paritaprevir and ritonavir in rat liver using deuterated internal standards (d8-paritapervir and d6-ritonavir). The method is linear from 20 to 20,000 and 5 to 10,000 pg on column for paritaprevir and ritonavir, respectively, and is normalized per milligram tissue. Interday and intraday variability ranged from 0.591 to 5.33% and accuracy ranged from -6.68 to 10.1% for quality control samples. The method was then applied to the measurement of paritaprevir and ritonavir in rat liver tissue samples from a pilot study.


CONCLUSIONS
The validated method is suitable for measurement of paritaprevir and ritonavir within rat liver tissue samples for PK studies.
Translational Pharmacology Research Core, Department of Pharmacy Practice, School of Pharmacy & Pharmaceutical Sciences, New York State Center of Excellence in Bioinformatics & Life Sciences, University at Buffalo, Buffalo, NY, USA.
Andrew J
AJ
Ocque
Translational Pharmacology Research Core, Department of Pharmacy Practice, School of Pharmacy & Pharmaceutical Sciences, New York State Center of Excellence in Bioinformatics & Life Sciences, University at Buffalo, Buffalo, NY, USA.
Colleen E
CE
Hagler
Translational Pharmacology Research Core, Department of Pharmacy Practice, School of Pharmacy & Pharmaceutical Sciences, New York State Center of Excellence in Bioinformatics & Life Sciences, University at Buffalo, Buffalo, NY, USA.
Robin
R
Difrancesco
Clinical & Translational Research Center, University at Buffalo, Buffalo, NY, USA.
Yvonne
Y
Woolwine-Cunningham
Translational Pharmacology Research Core, Department of Pharmacy Practice, School of Pharmacy & Pharmaceutical Sciences, New York State Center of Excellence in Bioinformatics & Life Sciences, University at Buffalo, Buffalo, NY, USA.
Cindy J
CJ
Bednasz
Translational Pharmacology Research Core, Department of Pharmacy Practice, School of Pharmacy & Pharmaceutical Sciences, New York State Center of Excellence in Bioinformatics & Life Sciences, University at Buffalo, Buffalo, NY, USA.
Gene D
GD
Morse
Division of Gastroenterology & Hepatology & Center for Clinical & Research in Liver Disease, Jacobs School of Medicine, University at Buffalo, Buffalo, NY, USA.
Andrew H
AH
Talal
D000818:Animals; D000998:Antiviral Agents / Q000032:analysis / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003521:Cyclopropanes; D016174:Hepacivirus / Q000187:drug effects / Q000201:enzymology; D006526:Hepatitis C / Q000188:drug therapy; D047029:Lactams, Macrocyclic; D057230:Limit of Detection; D008099:Liver / Q000378:metabolism*; D047028:Macrocyclic Compounds / Q000032:analysis / Q000493:pharmacokinetics*; D008297:Male; D010865:Pilot Projects; D011392:Proline / Q000031:analogs & derivatives; D011480:Protease Inhibitors / Q000032:analysis / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019438:Ritonavir / Q000032:analysis / Q000493:pharmacokinetics*; D013449:Sulfonamides; D053719:Tandem Mass Spectrometry / Q000379:methods*
D000998:Antiviral Agents; D003521:Cyclopropanes; D047029:Lactams, Macrocyclic; D047028:Macrocyclic Compounds; D011480:Protease Inhibitors; D013449:Sulfonamides; D011392:Proline; D019438:Ritonavir; C585405:paritaprevir
UPLC–MS/MS; core needle biopsy; fine needle aspirate; liver; paritaprevir; ritonavir; validation