Development and Validation of a New LC-MS/MS Analytical Method for Direct-Acting Antivirals and Its Application in End-Stage Renal Disease Patients.
Adult
Anilides
/ blood
Antiviral Agents
/ blood
Carbamates
/ blood
Chromatography, Liquid
/ methods
Cyclopropanes
Drug Stability
Female
Humans
Kidney Failure, Chronic
/ drug therapy
Lactams, Macrocyclic
Macrocyclic Compounds
/ blood
Male
Mass Spectrometry
/ methods
Middle Aged
Plasma
Proline
/ analogs & derivatives
Ritonavir
/ blood
Sulfonamides
Valine
Journal
European journal of drug metabolism and pharmacokinetics
ISSN: 2107-0180
Titre abrégé: Eur J Drug Metab Pharmacokinet
Pays: France
ID NLM: 7608491
Informations de publication
Date de publication:
Feb 2020
Feb 2020
Historique:
pubmed:
2
11
2019
medline:
25
9
2020
entrez:
1
11
2019
Statut:
ppublish
Résumé
The effectiveness of direct-acting antivirals (DAAs) is not well established in end-stage renal disease (ESRD) patients. Assessment of the plasma concentrations may support understanding of their therapeutic outcomes in this population. The aim of this study is to develop a direct, yet matrix-effect tolerant, analytical method for determining DAAs in the plasma of ESRD patients while maintaining a moderate cost per sample and with an improved analyte extraction recovery. In this study, a liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed for the analysis of ombitasvir (OMB), paritaprevir (PRT) and ritonavir (RIT) in plasma. Sample preparation was performed using the liquid-liquid extraction (LLE) method. Isocratic separation was performed using a mixture of methanol and 10 mM ammonium acetate (79:21, v/v) followed by MS/MS detection. The method was validated and applied to determine DAAs in the plasma of ESRD patients (n = 7). The developed method was linear (r An efficient analytical method for the determination of DAAs is presented. The method overcomes the potential analytical response fluctuation in ESRD. The developed method show improved extraction recoveries and is suitable for routine application in developing economies where hepatitis C virus is most prevalent.
Sections du résumé
BACKGROUND AND OBJECTIVE
OBJECTIVE
The effectiveness of direct-acting antivirals (DAAs) is not well established in end-stage renal disease (ESRD) patients. Assessment of the plasma concentrations may support understanding of their therapeutic outcomes in this population. The aim of this study is to develop a direct, yet matrix-effect tolerant, analytical method for determining DAAs in the plasma of ESRD patients while maintaining a moderate cost per sample and with an improved analyte extraction recovery.
METHODS
METHODS
In this study, a liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed for the analysis of ombitasvir (OMB), paritaprevir (PRT) and ritonavir (RIT) in plasma. Sample preparation was performed using the liquid-liquid extraction (LLE) method. Isocratic separation was performed using a mixture of methanol and 10 mM ammonium acetate (79:21, v/v) followed by MS/MS detection. The method was validated and applied to determine DAAs in the plasma of ESRD patients (n = 7).
RESULTS
RESULTS
The developed method was linear (r
CONCLUSIONS
CONCLUSIONS
An efficient analytical method for the determination of DAAs is presented. The method overcomes the potential analytical response fluctuation in ESRD. The developed method show improved extraction recoveries and is suitable for routine application in developing economies where hepatitis C virus is most prevalent.
Identifiants
pubmed: 31667795
doi: 10.1007/s13318-019-00584-6
pii: 10.1007/s13318-019-00584-6
doi:
Substances chimiques
Anilides
0
Antiviral Agents
0
Carbamates
0
Cyclopropanes
0
Lactams, Macrocyclic
0
Macrocyclic Compounds
0
Sulfonamides
0
ombitasvir
2302768XJ8
Proline
9DLQ4CIU6V
Valine
HG18B9YRS7
Ritonavir
O3J8G9O825
paritaprevir
OU2YM37K86
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
89-99Références
Blood Purif. 2017;43(1-3):179-188
pubmed: 28114143
AIDS. 2000 Jul 7;14(10):1333-9
pubmed: 10930147
Lancet. 2015 Jun 20;385(9986):2502-9
pubmed: 25837829
Am J Kidney Dis. 2017 Feb;69(2):228-236
pubmed: 27884475
J Chromatogr A. 2006 Mar 24;1109(2):253-66
pubmed: 16460742
Expert Rev Anti Infect Ther. 2014 Sep;12(9):1033-43
pubmed: 25074011
Br J Clin Pharmacol. 2017 Feb;83(2):269-293
pubmed: 27530469
Curr Drug Targets. 2017;18(7):851-862
pubmed: 26302808
AIDS. 1999 Jun 18;13(9):1099-107
pubmed: 10397541
Expert Opin Drug Metab Toxicol. 2014 Aug;10(8):1131-43
pubmed: 24961255
Clin Infect Dis. 2001 Aug 1;33(3):386-92
pubmed: 11438909
Drug Metab Dispos. 2016 Aug;44(8):1148-57
pubmed: 27179128
AIDS. 2001 Nov 9;15(16):2109-17
pubmed: 11684930
Sci Rep. 2018 Jan 26;8(1):1661
pubmed: 29374178
J Antimicrob Chemother. 2011 Aug;66(8):1673-86
pubmed: 21652618
Curr Opin Nephrol Hypertens. 2011 Sep;20(5):492-7
pubmed: 21788893
Drugs. 2015 Jun;75(9):1027-38
pubmed: 26059288
Antimicrob Agents Chemother. 2003 Mar;47(3):986-90
pubmed: 12604531
Am J Physiol Renal Physiol. 2007 Oct;293(4):F1238-47
pubmed: 17652373
AIDS. 2003 May 23;17(8):1157-65
pubmed: 12819517
Biochem Pharmacol. 2002 Nov 1;64(9):1355-74
pubmed: 12392818
Ther Drug Monit. 2018 Feb;40(1):1-8
pubmed: 29240615
J Pharm Biomed Anal. 2016 Jun 5;125:369-75
pubmed: 27131146
Gastroenterology. 2016 Jun;150(7):1590-1598
pubmed: 26976799
Drug Saf. 2016 Jul;39(7):589-611
pubmed: 27098247
Am J Kidney Dis. 2006 Jan;47(1):139-48
pubmed: 16377395
Bioanalysis. 2016 Jul;8(13):1353-63
pubmed: 27277877
BMC Nephrol. 2011 Jul 22;12:35
pubmed: 21777480
Hepatology. 2011 May;53(5):1742-51
pubmed: 21374691
Liver Int. 2014 Feb;34 Suppl 1:69-78
pubmed: 24373081
J Hepatol. 2015 Oct;63(4):805-12
pubmed: 26070406
Nat Rev Gastroenterol Hepatol. 2013 Oct;10(10):596-606
pubmed: 23817323
J Hepatol. 2016 Jun;64(6):1224-31
pubmed: 26829205
Clin Infect Dis. 2011 Apr 1;52(7):889-900
pubmed: 21427396
Anal Chem. 2003 Jul 1;75(13):3019-30
pubmed: 12964746
Semin Liver Dis. 2004;24 Suppl 2:47-54
pubmed: 15346246
J Chromatogr B Analyt Technol Biomed Life Sci. 2017 May 1;1052:103-109
pubmed: 28365413
Am J Kidney Dis. 2002 Feb;39(2 Suppl 1):S1-266
pubmed: 11904577
Mol Cell Biochem. 2004 Oct;265(1-2):57-61
pubmed: 15543934
Br J Clin Pharmacol. 2016 May;81(5):929-40
pubmed: 26710243