Adduct formation in quantitative bioanalysis: Effect of ionization conditions on paclitaxel

Abstract

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. (J Am Soc Mass Spectrom 2004, 15, 585-592)

Evaluation of different quantitative approaches for the determination of noneasily ionizable molecules by different atmospheric pressure interfaces used in liquid chromatography tandem mass spectrometry: Abamectin as case of study

“…Ammonium adducts present several advantages including usually easier fragmentation [15] and the possibility of using both API interfaces [16 -18]. Different primary amines also have been tested for this purpose [16].…”

Elimination Technique for Alkali Metal Ion Adducts from an Electrospray Ionization Process Using an On-line Ion Suppressor

“…6 Furthermore, Zhao et al, 7 Mortier et al, 2 and Karnes' group 8,9 reported the same usefulness of alkylamines for simvastatin, paclitaxel, and docetaxel, respectively. Teshima et al investigated an application of 1-alkylamines for quantitative analysis using LC/ESI-MS, [10][11][12] while other chemicals have been studied as well.…”

“…Generally, ESI-MS results in protonated molecules, [M+H] + , in the positive-ion mode; however, for some molecules the formation of alkali metal ion adducts, like [M+Na] + or [M+K] + , instead of proton addition are often observed. When the process is not controlled, facile adduct formation can lead to large variations and unreliable results during the quantitative method development of drugs with LC/ESI-MS. 1,2 Modulating the temperature or voltage for the ESI condition is insufficient to completely suppress the formation of alkali metal ion adducts. 3 Neubauer and Anderegg reported that the addition of sodium acetate to the HPLC mobile phase during an LC/ESI-MS experiment encourages the formation of sodium adduct ions.…”

“…Although Li and coworkers reported that the summation of the proton, ammonium and sodium ion adducts could provide more reproducible results for the quantification of ginkgolides or bilobalide, 1 the addition of the responses of the different MS/MS traces complicates matters when performing selective reaction monitoring (SRM). 2 In addition, the summation approach assumes that the response factor for all adduct ions is equal.…”

Quantitative structural characterization of phosphatidylinositol phosphates from biological samples

“…The benefit of addition of ammonium ion in mobile phases for signal enhancement and reproducible analysis was demonstrated by several groups using small chemicals (37,38). We wanted to identify PtdInsPs from biological samples such as cells and mice livers, and also to obtain the relative quantitation of PtdInsPs.…”