TY - JOUR
T1 - Determination of the HCV protease inhibitor telaprevir in plasma and dried blood spot by liquid chromatography-tandem mass spectrometry
AU - Verweij-Van Wissen, Corrien P W G M
AU - De Graaff-Teulen, Marga J A
AU - De Kanter, Clara T M M
AU - Aarnoutse, Rob E.
AU - Burger, David M.
PY - 2015/10/1
Y1 - 2015/10/1
N2 - Background: Telaprevir is a protease inhibitor used in the treatment of hepatitis C virus infection. Analytical methods for telaprevir should separate the compound from its R-diastereomer VRT-127394, which is 30-fold less active. The objective of this work was to develop liquid chromatography-tandem mass spectrometer (LC-MS/MS) assays for telaprevir both in plasma and in dried blood spot (DBS), capable of stabilizing the equilibrium and chromatographically separating the 2 epimers. Methods: Human plasma was acidified with formic acid and frozen within 1 hour after collection to stabilize the equilibrium between the 2 telaprevir diastereomers ex vivo in plasma. After protein precipitation, the sample was analyzed with LC-MS/MS. For the DBS assay, sampling paper was impregnated with citric acid solution to achieve stabilization of the epimers on the sampling paper. DBS samples were extracted before LC-MS/MS analysis. LC-MS/MS analysis comprised online solid-phase extraction and separation on a C18 column, with the mass spectrometer operating in TurboIonSpray-negative ionization mode and performing multiple reaction monitoring. Results: The assays were linear over the concentration range of 0.1-10 mg/L in plasma and DBS. Accuracies ranged from 97% to 106% in plasma and from 93% to 99% in DBS. Within- and between-day coefficients of variation were
AB - Background: Telaprevir is a protease inhibitor used in the treatment of hepatitis C virus infection. Analytical methods for telaprevir should separate the compound from its R-diastereomer VRT-127394, which is 30-fold less active. The objective of this work was to develop liquid chromatography-tandem mass spectrometer (LC-MS/MS) assays for telaprevir both in plasma and in dried blood spot (DBS), capable of stabilizing the equilibrium and chromatographically separating the 2 epimers. Methods: Human plasma was acidified with formic acid and frozen within 1 hour after collection to stabilize the equilibrium between the 2 telaprevir diastereomers ex vivo in plasma. After protein precipitation, the sample was analyzed with LC-MS/MS. For the DBS assay, sampling paper was impregnated with citric acid solution to achieve stabilization of the epimers on the sampling paper. DBS samples were extracted before LC-MS/MS analysis. LC-MS/MS analysis comprised online solid-phase extraction and separation on a C18 column, with the mass spectrometer operating in TurboIonSpray-negative ionization mode and performing multiple reaction monitoring. Results: The assays were linear over the concentration range of 0.1-10 mg/L in plasma and DBS. Accuracies ranged from 97% to 106% in plasma and from 93% to 99% in DBS. Within- and between-day coefficients of variation were
KW - Dried blood spot
KW - Liquid chromatography-tandem mass spectrometry
KW - Plasma
KW - Telaprevir
UR - http://www.scopus.com/inward/record.url?scp=84941898542&partnerID=8YFLogxK
U2 - 10.1097/FTD.0000000000000189
DO - 10.1097/FTD.0000000000000189
M3 - Article
C2 - 25627404
AN - SCOPUS:84941898542
SN - 0163-4356
VL - 37
SP - 626
EP - 633
JO - Therapeutic Drug Monitoring
JF - Therapeutic Drug Monitoring
IS - 5
ER -