Comparison of electrospray, atmospheric pressure chemical ionization, and atmospheric pressure photoionization in the identification of apomorphine, dobutamine, and entacapone phase II metabolites in biological samples
| Autor: | Leena Luukkanen, Risto Kostiainen, Eivor Elovaara, Helena Keski-Hynnilä, Jyrki Taskinen, Laurence Antonio, Mika Kurkela, Jacques Magdalou |
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| Rok vydání: | 2002 |
| Předmět: |
Male
Electrospray Spectrometry Mass Electrospray Ionization Apomorphine Electrospray ionization Catechols Atmospheric-pressure chemical ionization Photoionization Mass spectrometry 030226 pharmacology & pharmacy 01 natural sciences Analytical Chemistry Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Ionization Dobutamine Nitriles Animals Humans Chromatography High Pressure Liquid Ions Chemical ionization Chromatography Molecular Structure Chemistry 010401 analytical chemistry 0104 chemical sciences Rats Atmospheric Pressure Hepatocytes Microsomes Liver Glucuronide |
| Zdroj: | Analytical chemistry. 74(14) |
| ISSN: | 0003-2700 |
| Popis: | The applicability of different ionization techniques, electrospray ionization (ESI), atmospheric pressure chemical ionization (APCI), and a novel atmospheric pressure photoionization (APPI), were tested for the identification of the phase II metabolites of apomorphine, dobutamine, and entacapone in rat urine and in vitro incubation mixtures (rat hepatocytes and human liver microsomes). ESI proved to be the most suitable ionization method; it enabled detection of 22 conjugates, whereas APCI and APPI showed only 12 and 14 conjugates, respectively. Methyl conjugates were detected with all ionization methods. Glucuronide conjugates were ionized most efficiently with ESI. Only some of the glucuronides detected with ESI were detected with APCI and APPI. Sulfate conjugates were detected only with ESI. MS/MS experiments showed that the site of glucuronidation or sulfation could not be determined, since the primary cleavage was a loss of the conjugate group (glucuronic acid or SO3), and no site-characteristic product ions were formed. However, it may be possible to determine the site of methylation, since methylated products are more stable than glucuronides or sulfates. Furthermore, the loss of CH3 is not necessarily the primary cleavage, and site characteristic products may be formed. Identification and comparison of conjugates formed from the current model drugs were successfully analyzed in different biological specimens of common interest to biomedical research. A fairly good relation was obtained between the data from in vivo and in vitro models of drug metabolism. |
| Databáze: | OpenAIRE |
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