The effect of alkylamine additives on the sensitivity of detection for paclitaxel and docetaxel and analysis in plasma of paclitaxel by liquid chromatography–tandem mass spectrometry

Abstract

The formation of multiple molecular ions, especially due to sodium adduct ion formation, is commonly observed in electrospray mass spectrometry and may make reproducible and sensitive quantitation difficult. The objective of this work was to investigate the underlying mechanism involved in the suppression of multiple molecular ion formation and to improve the sensitivity of detection for the two anti-neoplastic agents paclitaxel and docetaxel. The results showed that alkylamine additives could significantly improve the detection of paclitaxel and docetaxel by suppression of multiple molecular ions through preferential formation of a predominant alkylamine adduct ion. Possible binding sites, binding interactions and binding competition were investigated for the sodium adduct and alkylamine adduct ions using various experimental techniques. The formation of a predominant amine adduct ion may be due to increased surface activity in the droplet. The optimal alkylamine for both analytes was octylamine, which increased peak heights of paclitaxel and docetaxel 4.8 and 3.7-fold (n = 3), respectively. The precision of the signals for the analytes was also improved 5.7-fold. A quantitative assay in plasma for paclitaxel was partially validated for the calibration range 1.0-1000 ng/mL (r = 0.9977) when using 0.05% octylamine as a reconstitution solution additive. The limit of detection (LOD) and limit of quantitation (LOQ) were 0.5 and 0.9 ng/mL, respectively. Acceptable precision, accuracy, specificity and sample stability were demonstrated for this assay. This approach may prove useful for other analytes with similar binding sites.

Chemical Reagents and Derivatization Procedures in Drug Analysis

“…Octylamine was particularly advantageous in improving the detectability of paclitaxel and docetaxel by about a factor of 4-5 down to about 0.5-1.0 ng mL −1 . (250) A similar enhancement was reported for a 3-benzothiepine compound TAK-778 using 1-hexylamine; interaction of the alkyl amine with the phosphoryl group was postulated. (251) Methylammonium acetate was effective in improving the MS sensitivity for simvastin and its hydroxy acid degradation product.…”

Sensitivity enhancement in liquid chromatography/atmospheric pressure ionization mass spectrometry using derivatization and mobile phase additives

“…One major molecular ion could be obtained with either dodecylamine/acetic acid (0.1 mM/0.1 mM) or acetic acid/sodium acetate (1.7 mM/20 M). Gao et al studied competition between the formation of [M + Na] + and [M + alkylamine + H] + including their binding sites and established a quantitation method for paclitaxel with LOD at 0.5 ng/mL [78].…”

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.…”