Chromatographic behavior of co-eluted plasma compounds and effect on screening of drugs by APCI-LC-MS(/MS):Applications to selected cardiovascular drugs

摘要

Chromatographic behavior of co-eluted compounds from un-extracted drug-free plasma samples was studied by LC-MS and LC-MS/MS with positive APCI.Under soft gradient,total ion chromatogram(TIC) consisted of two major peaks separated by a constant lower intensity region.Early peak(0.15-0.4 min) belongs to polar plasma compounds and consisted of smaller mass ions(m/z< 250);late peak(3.6-4.6 min) belongs to thermally unstable phospholipids and consisted of fragments with mlz<300.Late peak is more sensitive to variations in chromatographic and MS parameters.Screening of most targeted cardiovascular drugs at levels lower than 50 ng/mL has been possible by LC-MS for drugs with retention factors larger than three.Matrix effects and recovery,at 20 and 200 ng/mL,were evaluated for spiked plasma samples with 15 cardiovascular drugs,by MRM-LC-MS/MS.Average recoveries were above 90%and matrix effects expressed as percent matrix factor(%MF) were above 100%,indicating enhancement character for APCI.Large uncertainties were significant for drugs with smaller masses(m/z< 250) and retention factors lower than two.