| Summary: | 博士 === 國立臺灣大學 === 化學研究所 === 93 === Abstract
The ionization efficiency of several drugs have been improved by using chemical derivatization methods in negative ion atmospheric pressure chemical ionization (APCI) mode and anionic adduct ion formation methods in negative ion electrospray ionization (ESI) mode.
The analytes with acidic proton were derivatized with pentafluorobenzyl bromide ( PFB) for the electron capture capability under negative ion APCI conditions. The synthesized PFB-derivatives performed dissociative electron capture reaction and gave intense [M-181]- ions. The PFB-derivatization have been applied for three acidic drugs and the resulted [M-PFB]- ions expressed 10-25 fold higher sensitivity than the underivatized-drugs.
Two carbonyl compounds, nabumetone and testosterone, were derivatized with pentafluorophenyl hydrazine (PFPH) and analyzed by negative ion APCI. The PFPH-derivatives performed dissociative electron capture ionization and gave intense [M-HF]- ions in the mass spectra. In positive ion APCI, the PFPH-derivatives also performed efficient protonation and gave intense [M+H]+ ions in the mass spectra. In CID, the major product ions of the [M-20]- in negative ion APCI corresponded to the partial moiety of PFPH. On the contrary, the major product ions of [M+H]+ corresponded to the partial moiety of the analyte. In comparison with the detection limits of the underivatized analytes, the PFPH-derivatives expressed 2500-fold and 35-fold sensitivity enhancements for nabumetone and testosterone, respectively. By using the 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. The PFPH-derivatives were applied to the analysis of nabumetone and testosterone in human plasma by both negative ion APCI and positive ion APCI. The PFPH-derivatives in both ECAPCI and positive ion APCI were found to be capable of detecting 0.1 ng/ml of nabumetone in spiked plasma. For testosterone, endogenous testosterone in female plasma was detected in both negative ion APCI and positive ion APCI.
For several neutral drugs, mephenesin, guaifenesin, simvastatin, podophyllotoxin and inositol, the analysis was accomplished by negative ion ESI-MS using adduct formation with three different halide ions. The fluoride, chloride and bromide adducts of the selected drugs exhibited intense signals in negative ion ESI. Under collision-induced dissociation, the major product ions of bromide and chloride adducts were the nonspecific bromide and chloride anions, respectively. In contrast, fluoride adducts produced strong [M-H]- ions as well as product ions with good intensity. Fluoride attachment LC/ESI-MS/MS was applied to the analysis of the selected neutral drugs in human plasma. Detection limits in the range of 0.025-0.05 ng/mL were achieved using 0.5 mL plasma. Good linearity was observed for each of the drugs examined in human plasma over the range of 0.05-50 ng/mL.
Finally, two types of corona discharge adaptor were attached on the ESI probe tip for modifying or switching the ionization modes. By using the metal hanger to add a platinum discharge needle on the ESI probe tip, both the ESI and APCI can be performed simultaneously. On the other hand, by changing the metal hanger into a square metal casing, the ESI could be reduced form the mixed ESI/APCI source. The metal casing- discharge interface expressed almost the same ionization properties with the standard APCI interface. Good resistance to the plasma extracts was also observed by using the metal casing- discharge interface.
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