Validation of an electrospray ionisation LC–MS/MS method for quantitative analysis of telaprevir and its R-diastereomer

Validation of a sensitive LC/MS/MS method for the determination of telaprevir and its R‐isomer in human plasma

“…An analysis that compared quantitation in acidified vs nonacidified plasma that was subjected to room temperature for up to 8 h demonstrated that quantitation of telaprevir does not require acidification, while telaprevir-R does require acidification. Our results for telaprevir stability in patient samples were similar to the previous study of Penchala et al (2013), however telaprevir-R showed a more substantial change of concentrations in our study, possibly owing to longer exposure to room temperature. Our study also assessed more patient samples for the analysis.…”

“…The liquid-liquid extraction protocol yielded a recovery of 58.1-67.4% (mean 63.8%) for telaprevir and 51.4-60.9% (mean 57.1%) for telaprevir-R ( Table 2). The recoveries were below those reported in Penchala et al (2013) using a similar extraction technique, leading to recoveries of >90%. The reasons for this difference were not investigated further because the extraction produced accurate and precise results.…”

“…The MS/MS spectra were the same as that reported in previous studies (Farnik et al, 2009;Penchala et al, 2013) and telaprevir-R-IS had the same spectra as telaprevir-IS. Data acquisition, processing, and storage were performed using Xcalibur software, version 1.3 (Thermo Scientific, San Jose, CA, USA).…”

“…Our study also assessed more patient samples for the analysis. Penchala et al (2013) concluded that, in patient samples, the ratio of telaprevir/telaprevir-R changed significantly in nonacidified plasma, leading to the recommendation to use acidified plasma. Taken together, these findings show that telaprevir is stable in nonacidified patient samples when processed within 8 h, which enables new research focused on telaprevir, such as protein binding determinations, that was not possible previously when samples had to be acidified.…”

“…Given these pharmacologic characteristics, there is a potential role for therapeutic drug monitoring in the clinical use of telaprevir (Dolton et al, 2013). To facilitate clinical pharmacology studies of telaprevir, simple, fast and sensitive analytical methods are needed, but few methods are currently available (Farnik et al, 2009;D'Avolio et al, 2013;Penchala et al, 2013).…”