Development and validation of an UPLC-MS/MS bioanalytical method for simultaneous quantification of the antiretroviral drugs dolutegravir, elvitegravir, raltegravir, nevirapine and etravirine in human plasma

Contains fulltext : 202572.pdf (publisher's version ) (Closed access)Dolutegravir, elvitegravir, raltegravir, nevirapine and etravirine are antiretroviral drugs used as part of combined antiretroviral treatment for HIV-infection. For quantification of these drugs in human K2EDTA plasma samples an ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) bioanalytical method was developed and validated. Stable isotope labeled internal standards were used for each analyte. Simple protein precipitation with methanol was implemented to prepare plasma samples of at least 50muL. The method was validated for dolutegravir, elvitegravir, raltegravir, nevirapine and etravirine over the ranges 9.7-9700, 52-10,470, 9.7-9730, 73-14,680 and 15-3010ng/mL, respectively. Within-run and between-run accuracy and precision were within +/-15% of the nominal concentration for quality controls at high, medium and low concentrations, and within +/-20% at the lower limit of quantification for all analytes. Recovery was >/=76% and reproducible. Long-term stability of patient plasma samples was demonstrated for at least 12months at -40 degrees C (4months for etravirine). Currently, this robust method with a run time of 10min is used in clinical research and for therapeutic drug monitoring of these frequently used antiretroviral drugs

Development and validation of an UPLC-MS/MS bioanalytical method for simultaneous quantification of the antiretroviral drugs dolutegravir, elvitegravir, raltegravir, nevirapine and etravirine in human plasma

Dolutegravir, elvitegravir, raltegravir, nevirapine and etravirine are antiretroviral drugs used as part of combined antiretroviral treatment for HIV-infection. For quantification of these drugs in human K2EDTA plasma samples an ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) bioanalytical method was developed and validated. Stable isotope labeled internal standards were used for each analyte. Simple protein precipitation with methanol was implemented to prepare plasma samples of at least 50muL. The method was validated for dolutegravir, elvitegravir, raltegravir, nevirapine and etravirine over the ranges 9.7-9700, 52-10,470, 9.7-9730, 73-14,680 and 15-3010ng/mL, respectively. Within-run and between-run accuracy and precision were within +/-15% of the nominal concentration for quality controls at high, medium and low concentrations, and within +/-20% at the lower limit of quantification for all analytes. Recovery was >/=76% and reproducible. Long-term stability of patient plasma samples was demonstrated for at least 12months at -40 degrees C (4months for etravirine). Currently, this robust method with a run time of 10min is used in clinical research and for therapeutic drug monitoring of these frequently used antiretroviral drugs

Hedging Long-Term Forwards with Short-Term Futures: A Two-Regime Approach

In this paper we investigate Metallgesellschaft’s problem of hedging long-term forwards with short-term futures. Very different hedging strategies have been proposed in the literature. We attribute these differences to the underlying valuation approaches for oil futures and empirically compare five model-based hedging strategies. In particular, we consider a strategy which results from a two-regime pricing model. This continuous-time equilibrium model reflects the observation that prices of oil futures exhibit a very different behavior for low and high oil prices. Our empirical study shows that time diversification is the dominant effect for an effective hedging of long-term oil forwards with short-term futures. Copyright Kluwer Academic Publishers 2005long-term forwards, hedging, Metallgesellschaft case, two-regime pricing.,