A highly automated 96-well solid phase extraction and liquid chromatography/tandem mass spectrometry method for the determination of fentanyl in human plasma.

A high-throughput bioanalytical method based on automated sample transfer, automated solid phase extraction, and fast liquid chromatography/tandem mass spectrometry (LC/MS/MS) analysis, has been developed for the determination of the analgesic fentanyl in human plasma. Samples were transferred into 96-well plates using an automated sample handling system. Automated solid phase extraction (SPE) was carried out using a 96-channel programmable liquid-handling workstation using a mixed-mode sorbent. The extracted samples were then dried down, reconstituted and injected onto a silica column using an aqueous/organic mobile phase with tandem mass spectrometric detection. The method has been validated over the concentration range 0.05-100 ng/mL fentanyl in human plasma, based on a 0.25-mL sample size. The assay is sensitive, specific and robust. More than 2000 samples have been analyzed using this method. The automation of the sample preparation steps not only increased the analysis throughput, but also facilitated the transfer of the method between different bioanalytical laboratories of the same organization.

Shou WZ ，Jiang X ，Beato BD ，Naidong W ... -  《RAPID COMMUNICATIONS IN MASS SPECTROMETRY》

Automated 96-well solid phase extraction and hydrophilic interaction liquid chromatography-tandem mass spectrometric method for the analysis of cetirizine (ZYRTEC) in human plasma--with emphasis on method ruggedness.

Song Q ，Junga H ，Tang Y ，Li AC ，Addison T ，McCort-Tipton M ，Beato B ，Naidong W ... -  《JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES》

A rapid and sensitive liquid chromatography/negative ion tandem mass spectrometry method for the determination of an indolocarbazole in human plasma using 96-well diatomaceous earth plates for solid-liquid extraction [correction of using internal standard

A sensitive liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for the quantitation of a novel topoisomerase I inhibitor (indolocarbazole derivative I) in human plasma was developed to support clinical studies. Drug and internal standard were isolated from plasma by solid-liquid extraction using 96-well diatomaceous earth plates. Various extraction solvents were evaluated for extraction of I and 9% isopropyl alcohol (IPA) in methyl-tert-butyl ether (MtBE) was chosen as the optimal extraction solvent. The sensitivity of this LC/MS/MS method is 10x higher in negative ion mode using alkaline conditions than in positive ion mode using a wide range of pH's. A mobile phase with 2 mM ammonium hydroxide enhanced the sensitivity in negative ion mode over other volatile bases. The calibration curve for compound I is linear over the range 0.05-200 ng/mL in plasma and the lower limit of quantification (LLOQ) of the assay is 0.05 ng/mL, when 0.25 mL of plasma is processed. The method was fully validated and successfully applied to plasma samples from clinical studies. Performing chromatography at high pH, for enhanced negative ion sensitivity, eliminates the need for post-column addition of base. Furthermore, the 96-well diatomaceous earth plate extraction offers the following advantages over liquid-liquid extraction (LLE) or solid-phase extraction (SPE): clean sample extracts with reduced sample preparation time; increased sample throughput; no conditioning or washing steps; and a neutral eluate applicable to acid/base labile compounds.

Wang AQ ，Zeng W ，Musson DG ，Rogers JD ，Fisher AL ... -  《RAPID COMMUNICATIONS IN MASS SPECTROMETRY》

Quantitative determination of donepezil in human plasma by liquid chromatography/tandem mass spectrometry employing an automated liquid-liquid extraction based on 96-well format plates. Application to a bioequivalence study.

Apostolou C ，Dotsikas Y ，Kousoulos C ，Loukas YL ... -  《JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES》

High-throughput analysis of everolimus (RAD001) and cyclosporin A (CsA) in whole blood by liquid chromatography/mass spectrometry using a semi-automated 96-well solid-phase extraction system.

McMahon LM ，Luo S ，Hayes M ，Tse FL ... -  《RAPID COMMUNICATIONS IN MASS SPECTROMETRY》