Increasing bioanalytical throughput using pcSFC-MS/MS: 10 minutes per 96-well plate

被引:43
作者
Hoke, SH
Tomlinson, JA
Bolden, RD
Morand, KL
Pinkston, JD
Wehmeyer, KR
机构
[1] Procter & Gamble Co, Hlth Care Res Ctr, Mason, OH 45040 USA
[2] Procter & Gamble Co, Miami Valley Labs, Cincinnati, OH 45253 USA
关键词
D O I
10.1021/ac0014820
中图分类号
O65 [分析化学];
学科分类号
070302 ; 081704 ;
摘要
The utility of packed-column supercritical, subcritical, and enhanced fluidity liquid chromatographies (pcSFC) for high-throughput applications has increased during the past few years. In contrast to traditional reversed-phase liquid chromatography, the addition of a volatile component to the mobile phase, such as CO2, produces a lower mobile-phase viscosity. This allows the use of higher flow rates which can translate into faster analysis times. In addition, the resulting mobile phase is considerably more volatile than the aqueous-based mobile phases that are typically used with LC-MS, allowing the entire effluent to be directed into the MS interface. High-throughput bioanalytical quantitation using pcSFC-MS/MS for pharmacokinetics applications is demonstrated in this report using dextromethorphan as a model compound. Plasma samples were prepared by automated liquid/liquid extraction in the 96-well format prior to pcSFC-MS/MS analysis. Three days of validation data are provided along with study sample data from a patient dosed with commercially available Vicks 44, Using pcSFC and MS/MS, dextromethorphan was quantified in 96-well plates at a rate of similar to 10 min/plate with average intraday accuracy of 9% or better. Daily relative standard deviations (RSDs) were less than 10% for the 2.21 and 14.8 ng/mL quality control (QC) samples, while the RSDs were less than 15% at the 0.554 ng/mL QC level.
引用
收藏
页码:3083 / 3088
页数:6
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