Adduct formation in quantitative bioanalysis: effect of ionization conditions on paclitaxel.
Quantitative analysis of target compounds with liquid chromatography atmospheric pressure ionization mass spectrometry is sometimes hampered by adduct formation. In these situations, cationization with alkali metal ions instead of proton addition is often observed in the positive ion mode. This work studies the process of adduct formation and investigates potential strategies to control this phenomenon. Paclitaxel, a pharmaceutical chemotherapeutic agent, was used as a model compound. Electrospray (ESI), atmospheric pressure chemical ionization (APCI) and sonic spray ionization (SSI) are evaluated and compared. The work was performed on two different instruments, allowing the evaluation of different ionization behavior for different source design for electrospray, if any. Different mobile phase additives were compared, including acetic acid, formic acid, ammonium formate, and a range of primary amines. Continuous infusion was used for a fast screening, to detect optimal conditions. These were then further investigated in detail by LC-MS. The results indicate that electrospray is the more sensitive interface for this compound on the investigated apparatus. Unacceptable quantitative data were acquired without additives in the mobile phase. Generally, additives increased the reproducibility significantly. A response of mainly one ion was achieved with dodecylamine/acetic acid and acetic acid/sodium acetate. The data also point out the importance of evaluating adduct formation for compounds prone to this phenomenon during method development, especially in view of accurate quantitation.
Mortier
Kjell A
KA
Laboratory of Toxicology, Ghent University, Ghent, Belgium.
Zhang
Guo-Fang
GF
van Peteghem
Carlos H
CH
Lambert
Willy E
WE
D000588:Amines / Q000737:chemistry; D007477:Ions / Q000737:chemistry; D013058:Mass Spectrometry / Q000379:methods*; D015394:Molecular Structure; D017239:Paclitaxel / Q000032:analysis* / Q000737:chemistry*; D013329:Structure-Activity Relationship
D000588:Amines; D007477:Ions; D017239:Paclitaxel