Identification of diphenhydramine metabolites in human urine by capillary electrophoresis-ion trap-mass spectrometry.

The identification of diphenhydramine (DH) metabolites that are frequently observed in the capillary zone electrophoresis (CZE) and micellar electrokinetic capillary chromatography (MEKC) analyses of alkaline liquid/liquid and solid-phase extracts of patient urines is demonstrated. Having standards for DH and diphenhydramine-N-oxide (DHNO), the presence of these two compounds could be confirmed in urines that were collected overnight after administration of 25 mg DH chloride. Using CZE coupled to ion-trap mass spectrometry (CE-MS(n)) with positive electrospray ionization and an acetate buffer at pH 5.

Assessment of the stereoselective metabolism of methaqualone in man by capillary electrophoresis.

Methaqualone (MQ) and its hydroxylated metabolites are quinazoline derivatives that exhibit atropisomerism. As a continuation of our previous work with these compounds (Electrophoresis 2001, 22, 3270-3280), chiral capillary zone electrophoresis with hydroxypropyl-beta-cyclodextrin as buffer additive and multiwavelength absorbance detection is shown to be an effective tool to provide insight into the stereoselectivity of the MQ metabolism. The five major monohydroxy MQ metabolites formed during biotransformation do not show enantiomerization at temperatures up to 85 degrees C.

Capillary electrophoresis to assess drug metabolism induced in vitro using single CYP450 enzymes (Supersomes): application to the chiral metabolism of mephenytoin and methadone.

Capillary electrophoresis (CE) with multiwavelength absorbance detection is demonstrated to be an effective tool for the assessment of in vitro drug metabolism studies using microsomes containing single human cytochrome P450 enzymes (CYPs) expressed in baculovirus-infected insect cells (Supersomes). Mephenytoin (MEPH), dextromethorphan, diclofenac, caffeine, and methadone (MET) were successfully applied as test substrates for CYP2C19, CYP2D6*1, CYP2C9*1, CYP1A2, and CYP3A4, respectively. For each system, the CE-based assay could be shown to permit the simultaneous analysis of the parent drug and its targeted metabolite.

Capillary electrophoresis with (R)-(--)-N-(3,5-dinitrobenzoyl)-alpha-phenylglycine as chiral selector for separation of albendazole sulfoxide enantiomers and their analysis in human plasma.

The electrokinetic separation and analysis of the enantiomers of albendazole sulfoxide (ABZSO), a sulfoxide with a sulfur stereogenic center hepatically formed during therapy with the anthelmintic drug albendazole (ABZ), is reported. Using aqueous or nonaqueous alkaline background electrolytes, ABZSO enantiomers cannot be separated via single use of common neutral cyclodextrins and negatively charged carboxymethyl-beta-cyclodextrin. With the Pirkle-type (R)-(-)-N-(3,5-dinitrobenzoyl)-alpha-phenylglycine ((R)-DNBPG) chiral selector, however, ABZSO enantiomers do separate within a borate background electrolyte of pH 9.