Elimination of isobaric interference and signal-to-noise ratio enhancement using on-line mobile phase filtration in liquid chromatography/tandem mass spectrometry.

Rationale: Liquid chromatography/tandem mass spectrometry (LC/MS/MS) instruments are selective and sensitive but can still be affected by isobaric interference or chemical noise arising from multiple sources such as the mobile phase. In this study, a high-performance liquid chromatography (HPLC) on-line mobile phase filtration setup is described and used to remove interference to allow better detection of the analyte of interest.

Methods: For instance, a filtration device containing a chemical sorbent is installed at the HPLC outlet of the aqueous solvent pump A or the organic solvent pump B.

Impact of methylation of acyl glucuronide metabolites on incurred sample reanalysis evaluation: ramiprilat case study.

Background: Reanalysis of incurred samples showed that the bioanalytical method for the quantification of ramipril and ramiprilat was generating irreproducible results for ramiprilat.

Results: An additional peak interfering with ramiprilat was observed in the incurred samples but not in the calibrant and quality control samples. A similar interference was detected for ramipril, but it was chromatographically separated.

Elimination of LC-MS/MS matrix effect due to phospholipids using specific solid-phase extraction elution conditions.

Background: The objective is to find elution conditions using different solid-phase extraction chemistries to reduce the amount of phospholipids in plasma extract, which is associated with matrix effect in LC-MS.

Results: Phospholipids' recovery was reduced by decreasing the eluents' methanol content applied to silica-based and polymer-based reversed-phase solid-phase extraction cartridges while 100% acetonitrile applied to the silica-based cartridges drastically minimized the phospholipids' elution. Silanol interactions are involved in the increased retention of phospholipids with silica-based reversed-phase cartridges when using high percentages of ACN in eluents.

Effect of high pH mobile phase on the sensitivity of multiple drugs by LC positive electrospray ionization MS/MS.

Background: In this study, the postcolumn addition approach was used to evaluate the impact of high pH modifiers on the sensitivity of 25 compounds by LC-MS/MS under positive ESI (ESI+).

Results: None of the compounds were significantly suppressed by the use of high pH modifiers. Most of them showed a signal enhancement by at least twofold compared with acidic modifiers.