Evaluation of several solid phase extraction liquid chromatography/tandem mass spectrometry on‐line configurations for high‐throughput analysis of acidic and basic drugs in rat plasma

Abstract

Several configurations using 6- and 10-port switching valves were studied for high flow, on-line extraction of rat plasma coupled to an electrospray triple quadrupole mass spectrometer. Each plasma sample was diluted 1:1 with an aqueous internal standard solution. The sample was injected into a 2.1 x 20 mm cartridge column packed with 25 microm divinylbenzene/N-vinylpyrrolidone packing using 100% aqueous mobile phase at 4 mL/min. After sample loading and sample cleanup, the analytes were eluted from the extraction column with a 1.0-min gradient at 0.4 mL/min. The samples were either analyzed directly after elution from the extraction column or after additional separation using a short high performance liquid chromatography (HPLC) column. The different configurations were tested using an acidic drug (diflunisal) and a basic drug (clemastine) in rat plasma. On-line analysis was performed by injecting 200 microL of diluted plasma. The mass spectrometer was operated in the multiple reaction monitoring (MRM) mode. All calibration standards gave relative standard deviations (RSDs) below 5%. The total time per sample was 3 min.

An automated on-line method for simultaneous analysis of phenothiazines in human serum by high-performance liquid chromatography/sonic spray ionization mass spectrometry using backflush column switching

“…The time required for column washing and reequilibration after target drug elution is also an important factor when many samples are analyzed. The Oasis HLB cartridge used as the precolumn in this study is packed with copolymer, poly(divinylbenzen-co-N-vinylpyrrolidone), which exhibits both hydrophilic and lipophilic retention characteristics, and enabled direct injection of crude biological samples [13,[29][30][31][32][33][34][35][36][37][38]. Furthermore, the large particles of sorbent material in the column enabled very high fl ow rates of mobile phases [13].…”

Restricted access materials and large particle supports for on-line sample preparation: an attractive approach for biological fluids analysis

“…Xia et al [189] developed a high-throughput method which allowed the analysis of guanidine drugs in plasma injected in two LPS extraction supports coupled to an octadecyl analytical column in less than 2 min. A similar process was applied for the determination of acidic and basic drugs in plasma [190].…”

Fast LC/MS in the analysis of small molecules

“…Excellent results are obtained, and column lifetimes are adequate due to the use of the larger particles. Mallet [64] modified the procedure published by Ayrton [62,63] using a 20 mm×2.1 mm column packed with a 25-µm polymeric packing. The sample is still loaded and washed at high flow (4 mL min -1 ).…”