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.
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.
Liang
H R
HR
Tandem Labs, A Division of NWT Inc., Salt Lake City, UT 84124, USA. hairui@tandemlabs.com
Foltz
R L
RL
Meng
M
M
Bennett
P
P
D016477:Artifacts; D002138:Calibration; D002853:Chromatography, Liquid; D017022:Flow Injection Analysis / Q000379:methods*; D005632:Fructose / Q000032:analysis / Q000097:blood / Q000737:chemistry; D006801:Humans; D007553:Isotope Labeling / Q000379:methods* / Q000592:standards; D008691:Methadone / Q000032:analysis / Q000097:blood / Q000737:chemistry; D004364:Pharmaceutical Preparations / Q000032:analysis* / Q000097:blood / Q000737:chemistry*; D011786:Quality Control; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013012:Sorbitol / Q000032:analysis / Q000097:blood / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*
D004364:Pharmaceutical Preparations; D005632:Fructose; D013012:Sorbitol; D008691:Methadone