Comparison of Atmospheric Pressure Chemical Ionization, Electrospray Ionization, and Atmospheric Pressure Photoionization for the Determination of Cyclosporin A in Rat Plasma

Abstract

Atmospheric pressure chemical ionization was compared with electrospray ionization and atmospheric pressure photoionization (APPI) as an interface of high-performance liquid chromatography (HPLC)-tandem mass spectrometry (MS/MS) for the determination of cyclosporin A (CsA) in biological fluids in support of in vivo pharmacodynamic studies. These ion sources were investigated in terms of their suitability and sensitivity for the detection of CsA. The effects of the eluent flow rate and composition as well as the nebulizer temperatures on the photoionization efficiency of CsA in the positive ion mode under normal-phase HPLC conditions were explored. The ionization mechanism in the APPI environment with and without the use of the dopant was studied using two test compounds and a few solvent systems employed for normal-phase chromatography. The test compounds were observed to be ionized mainly by proton transfer with the self-protonated solvent molecules produced through photon irradiation. Furthermore, ion suppression due to sample matrix interference in the normal-phase HPLC-APPI-MS/MS system was monitored by the postcolumn infusion technique. The applicability of these proposed HPLC-API-MS/MS approaches for the determination of CsA at low nanogram per milliliter levels in rat plasma was examined. These proposed methods were then compared with respect to specificity, linearity, detection limit, and accuracy.

Atmospheric Pressure Photoionization as a Powerful Tool for Large-Scale Lipidomic Studies

“…Nevertheless, more polar compounds soluble in water/methanol mixture (i.e., steroids [18], peptides [19,20], quaternary ammonium salts [21], oligosaccharides [22], or oligodeoxyribonucleotides [23]) are also ionizable with APPI. This feature enables the efficient coupling of both reverse-phase and normal-phase liquid chromatography with APPI-MS [24]. These two chromatographic modes are frequently used to analyze lipids.…”

Comparison of atmospheric pressure photoionization and ESI for CZE‐MS of drugs

“…These species often cannot be ionized by ESI or atmospheric pressure chemical ionization. During the latter years, LC-APPI-MS of a wide range of compounds, including steroids [15], antibiotics [16], flavonoids [17] and other pharmaceutical compounds [18,19] has been reported. The feasibility of APPI for CZE-MS was indicated by Nilsson et al [20], and studied in more detail in our laboratory [21].…”

The Role of Liquid Chromatography–Mass Spectrometry in Pharmacokinetics and Drug Metabolism

“…Toward this end, electrospray ionization (ESI), atmospheric pressure chemical ionization (APCI), and atmospheric pressure photo-ionization (APPI) have proven valuable for both qualitative and quantitative screening of small molecules (e.g., pharmaceutical products) [9][10][11][12][13][14].…”