Ionization enhancement in atmospheric pressure chemical ionization and suppression in electrospray ionization between target drugs and stable‐isotope‐labeled internal standards in quantitative liquid chromatography/tandem mass spectrometry

Abstract

The phenomena of ionization suppression in electrospray ionization (ESI) and enhancement in atmospheric pressure chemical ionization (APCI) were investigated in selected-ion monitoring and selected-reaction monitoring modes for nine drugs and their corresponding stable-isotope-labeled internal standards (IS). The results showed that all investigated target drugs and their co-eluting isotope-labeled IS suppress each other's ionization responses in ESI. The factors affecting the extent of suppression in ESI were investigated, including structures and concentrations of drugs, matrix effects, and flow rate. In contrast to the ESI results, APCI caused seven of the nine investigated target drugs and their co-eluting isotope-labeled IS to enhance each other's ionization responses. The mutual ionization suppression or enhancement between drugs and their isotope-labeled IS could possibly influence assay sensitivity, reproducibility, accuracy and linearity in quantitative liquid chromatography/mass spectrometry (LC/MS) and liquid chromatography/tandem mass spectrometry (LC/MS/MS). However, calibration curves were linear if an appropriate IS concentration was selected for a desired calibration range to keep the response factors constant.

Simultaneous determination of diphenylarsinic and phenylarsinic acids in amended soils by optimized solvent extraction coupled to HPLC–MS/MS

“…In contrast, only with disodium hydrogen phosphate extraction was a limited matrix effect (102% ≤ ME ≤ 107%, CV ≤ 3%) obtained for PAA as presented in Table 4. The higher matrix tolerance of DPAA than of PAA may possibly be associated with the comparatively longer retention time of DPAA (19.3 min) than PAA (11.4 min), as sufficient chromatographic separation in the quantitative determination of analytes is recommended to avoid possible co-elution with interfering substances (Liang et al, 2003).…”

Electrospray Ionization Mass Spectrometry for the Quantification of Inorganic Cations and Anions

“…To minimize matrix effects, various approaches, including on-line or off-line sample separation using chromatographic techniques, [20][21][22][23][24] liquid-liquid extraction, 21 and use of nanospray 25 have been described and reviewed. [26][27][28] Evaluations based on the relative signal intensities using internal standards, which are typically stable isotope-labeled analogues or compounds having similar structures to the analytes, are also effective in diminishing the matrix effect, 20,22,23 but this may not always be applicable. 29 Nevertheless, the matrix effect is strongly dependent on the chemical nature of each sample, so there is no universal approach that minimizes or overcomes the matrix effect.…”

Reverse-Polynomial Dilution Calibration Methodology Extends Lower Limit of Quantification and Reduces Relative Residual Error in Targeted Peptide Measurements in Blood Plasma

“…There are a few possibilities to this phenomenon. First, as the analyte and C13N15-labeled analog chromatographically co-elute, they too experience competitive ionization against each other in the ESI droplet: this may be a function of the concentration of the analyte and stable isotope analog (affecting the analyte/ isotope analog/solvent ratio of the droplet), the hydrophobicity of the analyte (affecting the overall positioning and aggregation of analyte/stable-isotope analogs in the droplet) or the chromatography flow rate (affecting the amount of excess charge on the droplet surface), among other LC-MS/MS parameters (33,34). Furthermore, it has been noted in the small molecule setting that the presence of a complex matrix can alter the analyte and internal standard signals to a different degree, possibly as a result of the sample matrix altering interactions of the analyte/stable isotope analog with organic mobile phase (20,(35)(36)(37).…”

“…Furthermore, it has been noted in the small molecule setting that the presence of a complex matrix can alter the analyte and internal standard signals to a different degree, possibly as a result of the sample matrix altering interactions of the analyte/stable isotope analog with organic mobile phase (20,(35)(36)(37). Ultimately however, why there is a difference in ESI-LC-MS/MS experience in some analytes and their C13N15 labeled counterparts is multifactorial and remains under investigation (20,(33)(34)(35)(36)(37). These elements should not impede quantitative accuracy if precision is high (low CV%) within samples of the same matrix, and indeed in this dataset, once a complex matrix was introduced, the matrix peak area ratio-to-heavy response factor, although significantly different from the no-matrix (neat) response factor, remained highly stable across matrices (Table IV).…”