Application of pentafluorophenyl hydrazine derivatives to the analysis of nabumetone and testosterone in human plasma by liquid chromatography?atmospheric pressure chemical ionization?tandem mass spectrometry

Abstract

Two carbonyl compounds, nabumetone and testosterone, were derivatized with pentafluorophenyl hydrazine (PFPH) and analyzed by atmospheric-pressure chemical-ionization mass spectrometry. The PFPH derivatives underwent dissociative electron capture in negative-ion APCI (ECAPCI) and gave intense [M-20](-) ions in the mass spectra. In positive-ion APCI, the PFPH derivatives underwent efficient protonation and gave intense [M + H](+) ions in the mass spectra. In CID, the major product ions of the [M-20](-) ions in ECAPCI corresponded to the partial moiety of PFPH. In contrast, the major product ions of [M + H](+) corresponded to the partial moiety of the analyte. By using selected reaction monitoring (SRM) detection, low pg of nabumetone (1 pg) and testosterone (7 pg) could be detected in both ECAPCI and positive-ion APCI. In comparison with the detection limits (SRM) of the underivatized analytes, use of the PFPH derivatives resulted in 2500-fold and 35-fold sensitivity enhancements for nabumetone and testosterone, respectively. The PFPH derivatives were applied to the analysis of nabumetone and testosterone in human plasma by both ECAPCI and positive-ion APCI and were found to enable detection of 0.1 ng mL(-1) nabumetone in spiked plasma. For testosterone, endogenous testosterone in female plasma was detected in both ECAPCI and positive-ion APCI.

A General and Efficient Heterogeneous Gold‐Catalyzed Hydration of Nitriles in Neat Water under Mild Atmospheric Conditions

“…All the tested compounds presented a neutral loss of 181 amu (C 6 F 5 N) among other ions. This type of fragmentation was previously observed in other studies when analyzing pentafluorobenzylhydroxylamine PFBHA38, 39 and PFPH derivatives of carbonyl compounds 32, 33. Neutral loss scans were performed in order to confirm the previous results and 19 of the 24 compounds under study were detected under neutral loss scanning of 181 amu.…”

“…Derivatization of the carbonyl groups was adapted from other studies32, 33 and was performed as follows: 200 µl of 100 m M PFPH in methanol was added to 600 µl of a carbonyl solution (maximum carbonyl functional group concentration level was 1 m M ) and the mixture was left to react for 18 h at room temperature. Extending the reaction time over 18 h was tested on four compounds (A1, A6, K1 and K5) but did not show any significant improvement in terms of signal intensity.…”

Analysis of steroid estrogens in water using liquid chromatography/tandem mass spectrometry with chemical derivatizations

“…Therefore, the product ions and collision energies for the derivatized estrogens were identical to the underivatized ones (Table 2). The position of the corona discharge needle and its current were critical in the electron‐capture process;17, 35 the intensity increased as the current increased. However, the maximum discharge current of the mass spectrometer (TSQ 7000) was 10 µA, and the corona probe position fixed.…”

High‐throughput LC‐MS/MS assay for 6‐methoxy‐2‐naphthylacetic acid, an active metabolite of nabumetone in human plasma and its application to bioequivalence study

“…Most of the earlier reports employ liquid-liquid extraction (LLE) using n-hexane-dichloromethane (Sheen and Her, 2004), diethyl ether (Nobilis et al, 2004) and ethyl acetate (Kobylinska et al, 2003), except for the work of Nobilis et al (2003), where they carried out sample preparation with SPE as well as LLE. The recoveries obtained with SPE in the present study were not quantitative but were consistent and reproducible.…”

“…In another report (Nobilis et al, 2004), they identified and determined phase II nabumetone metabolites by HPLC with photodiode array and mass spectrometric detection. A method for simultaneous determination of nabumetone and testosterone in human plasma after derivatization with pentafluorophenyl hydrazine has been presented (Sheen and Her, 2004). The analysis was done by liquid chromatography-atmospheric pressure-chemical ionization mass spectrometry (LC-APCI-MS) in the positive and negative ionization modes, but the run time achieved in their study was too high to be used for routine sample analysis.…”