Hye-Ki Min

Determination of amphetamine, methamphetamine and dimethamphetamine in Human Urine by Solid-Phase Microextraction (SPME)-Gas Chromatography/Mass Spectrometry

A simple and rapid assay method for three stimulant drugs (amphetamine, methamphetamine, and dimethamphetamine) in human urine using solid-phase microextraction was developed. In solid-phase microextraction, the drugs were equilibrated between the adsorbent coated-fiber and aqueous sample matrix. After adsorption of the analytes, the fiber was directly transferred to the injector of a gas chromatograph, where the analytes were thermally desorbed and subsequently separated by the gas chromatograph and detected by mass spectrometer. The solid-phase microextraction method, which did not require solvents, was found to be a fast and simple analytical method. We optimized the solid-phase microextraction technique, for factors such as the NaCl salt effect (30%), pH effect (pH=12.4), equilibration time (30 min), desorption time (1 min) and coated-fiber type (100 microm poly(dimethylsiloxane)) and detected the stimulants in human urine, obtained from human subjects. The detection limits of each drug were below 1-10 ng/ml. The developed method can be applied to the abused drug test.

Absorption, distribution, metabolism, and excretion of CKD-732, a novel antiangiogenic fumagillin derivative, in rats, mice, and dogs

The pharmacokinetics of CKD-732 (6-0-4-[dimethyl-aminoethoxy)cinnamoyl]-fumagillol hemioxalate) was investigated in male SD rats and beagle dogs after bolus intravenous administration. The parent compound and metabolites obtained fromin vitro andin vivo samples were determined by LC/MS. The main metabolite was isolated and identified as anN-oxide form of CKD-732 by NMR and LC/MS/MS. CKD-732 was metabolized into eitherM11 or others by rapid hydroxylation, demethylation, and hydrolysis. The blood level following the intravenous route declined in first-order kinetics with T1/2β values of 0.72~0.78 h for CKD-732 and 0.92~1.09 h forM11 in rats at a dose of 7.5-30 mg/kg. In dogs, T1/2β values of CKD-732 andM11 were 1.54 and 1.79 h, respectively. Moreover, AUC values increased dose dependently for CKD-732 andM11 in rats and dogs. The CLtot and Vdss did not change significantly with increasing dose, indicating linear pharmacokinetic patterns. The excretion patterns through the urine, bile, and feces were also examined in the animals. The total amount excreted in urine, bile, and feces was 2.13% for CKD-732 and 1.29% forM11 in rats, and 1.58% for CKD-732 and 2.28% forM11 in dogs.

Identification of IY81149 and its metabolites in the rat plasma using the on-line HPLC/ESI mass spectrometry

Reversed-phase high-performance liquid chromatography/mass spectrometry (HPLC/MS) with an electrospray ionization (ESI) interface was applied to the identification of metabolites of IY 81149 in the rat plasma. Fragments obtained using collision-induced dissociation (CID) in both positive and negative modes were utilized to elucidate the structure of metabolites. The eluent from the conventional HPLC column was split and directly introduced into an ESI-mass spectrometer for the identification of the structures. The CID technique allowed the sensitive identification of sulfonyl-IY81149 and hydroxy-IY81149 from the rat plasma.

Characterization of amiodarone metabolites and impurities using liquid chromatography/atmospheric pressure chemical ionization mass spectrometry

Using the high performance liquid chromatography/atmospheric pressure chemical ionization tandem mass spectrometry (HPLC/APCI-MS/MS) technique, together with established trends from the literature, the structures of metabolites and impurities of amiodarone, an anti-arrhythmic drug, have been assigned. By comparing analyses of products of incubation with rat liver microsomes with controls in which glucose 6-phosphate dehydrogenase was omitted, metabolites could be distinguished from impurities. Structures for the two proposed metabolites and four impurities are proposed.