Hui-Hyun Kim

Wonkwang University, Iksan, North Jeolla, South Korea

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Publications (7)16.76 Total impact

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    ABSTRACT: A rapid, sensitive and selective hydrophilic interaction liquid chromatography-tandem mass spectrometric (HILIC-MS/MS) method for the determination of levofloxacin in human plasma was developed. Levofloxacin and ciprofloxacin (internal standard) were extracted from human plasma with dichloromethane and analyzed on an Atlantis HILIC Silica column with the mobile phase of acetonitrile-ammonium formate (100 mM, pH 6.5) (82:18 v/v). The analytes were detected using an electrospray ionization tandem mass spectrometry in the multiple-reaction-monitoring mode. The standard curve was linear (r>0.999) over the concentration range of 10.0-5000 ng/ml. The lower limit of quantification for levofloxacin was 10.0 ng/ml using 20 microl plasma sample. The coefficient of variation and relative error for intra- and inter-assay at four QC levels were 2.9-7.8% and -7.3% to -2.2%, respectively. The recoveries of levofloxacin and ciprofloxacin were 55.2% and 77.3%, respectively. This method was successfully applied to the pharmacokinetic study of levofloxacin in humans.
    Journal of Pharmaceutical and Biomedical Analysis 06/2006; 41(2):622-7. · 2.95 Impact Factor
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    ABSTRACT: A rapid, sensitive and selective method for the determination of gabapentin in human plasma was developed using hydrophilic interaction liquid chromatography/tandem mass spectrometry (HILIC/MS/MS). The devised method involved protein precipitation with acetonitrile followed by separation on an Atlantis HILIC silica column using an acetonitrile/ammonium formate mobile phase (100 mM, pH 3.0) (85:15, v/v). Analytes were detected using an electrospray ionization mass spectrometer in the multiple-reaction monitoring mode. The standard curve was linear (r = 1.000) over the concentration range of 50.0-10000 ng/mL. The lower limit of quantification for gabapentin was 50.0 ng/mL (ca. 20 pg gabapentin) using a 10-microL plasma sample. The coefficients of variation and relative errors for intra- and inter-assay at four QC levels (i.e., 50.0, 125, 750, and 7500 ng/mL) were 4.7 to 9.4% and -4.1 to 1.6%, respectively. Absolute and relative matrix effects for gabapentin and metformin were practically absent. Gabapentin and metformin recoveries were 98.5% and 99.0%, respectively. This method was successfully applied to a bioequivalence study of gabapentin in humans.
    Rapid Communications in Mass Spectrometry 02/2006; 20(14):2127-32. · 2.51 Impact Factor
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    ABSTRACT: KR-31831 ((2S,3R,4S)-4-(((1H-imidazol-2-yl)methyl)(4-chlorophenyl)amino)-6-amino-2-(dimethoxymethyl)-2-methyl-3,4-dihydro-2H-chromen-3-ol) is a novel antiangiogenic agent. In vitro and in vivo metabolism of KR-31831 in rats has been investigated using LC-MS and LC-MS/MS analysis. Incubation of rat liver microsomes and hepatocytes with KR-31831 produced three metabolites (M1-M3). M1, M2, and M3 were identified as N-((1H-imidazol-2-yl)methyl)-4-chlorobenzenamine, (2R,3R,4S)-4-(((1H-imidazol-2-yl)methyl)(4-chlorophenyl) amino)-6-amino-2-(hydroxymethyl)-2-methyl-3,4-dihydro-2H-chromen-3-ol, and N-((2S,3R,4S)-4- (((1H-imidazol-2-yl)methyl)(4-chlorophenyl)amino)-2-(dimethoxymethyl)-3-hydroxy-2-methyl-3,4-dihydro-2H-chromen-6yl)acetamide, respectively, by co-chromatography with the authentic standards and by comparison with product ion spectra of the authentic standards. Those in vitro metabolites were also detected in bile, plasma, or urine samples after an intravenous administration of KR-31831 to rats. The metabolic routes for KR-31381 included the metabolism of acetal group to hydroxymethyl group (M2), N-dealkylation to M1, and N-acetylation at the 6-amino group (M3).
    Journal of Separation Science 10/2005; 28(14):1818-22. · 2.59 Impact Factor
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    ABSTRACT: KR-60436 ([1-(4-methoxy-2-methylphenyl)-4-[(2-hydroxyethyl)amino]-6-trifluoromethoxy-2,3-dihydropyrrolo [3,2-c]quinoline]) is a new reversible H+/K+-ATPase inhibitor. The isoforms of human liver cytochrome P450 (CYP) responsible for the hepatic transformation of KR-60436 is identified. Dihydropyrrole oxidation and O-demethylation are major pathways for the metabolism of KR-60436 in human liver microsomes, whereas N-dehydroxyethylation and hydroxylation are minor pathways. The specific CYP isozymes responsible for KR-60436 oxidation to four major metabolites, pyrrole-KR-60436, O-demethylpyrrole-KR-60436, N-dehydroxyethyl-KR-60436 and an active metabolite, O-demethyl-KR-60436 were identified using the combination of correlation analysis, immuno-inhibition, chemical inhibition in human liver microsomes and metabolism by expressed recombinant CYP enzymes. The inhibitory potency of KR-60436 on clinically major CYPs was investigated in human liver microsomes. The results show that CYP3A4 contributes to the oxidation of KR-60436 to pyrrole-KR-60436, O-demethylpyrrole-KR-60436 and N-dehydroxyethyl-KR-60436, and CYP2C9 and CYP2D6 play roles in demethylation of KR-60436 to form the active metabolite, O-demethyl-KR-60436. KR-60436 was found to inhibit potently the metabolism of CYP1A2 substrates.
    Toxicology Letters 02/2005; 155(1):103-14. · 3.15 Impact Factor
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    ABSTRACT: A rapid, sensitive and selective liquid chromatography-tandem mass spectrometric (LC-MS/ MS) method for the determination of lithospermic acid B (LSB) in rat serum was developed. LSB and internal standard, 7-hydroxy-3-phenyl-chromen-4-one (HPC) were extracted from rat serum with methyl-tert-butyl ether at acidic pH and analyzed on a Luna C8 column with the mobile phase of acetonitrile-ammonium formate (10 mM, pH 6.5) (50:50, v/v). The analytes were detected using a negative electrospray ionization tandem mass spectrometry in the multiple-reaction-monitoring mode. The standard curve was linear (r2= 0.997) over the concentration range of 10.0-500 ng/mL. The coefficient of variation and relative error for intra- and interassay at three QC levels were 1.1 approximately 6.2% and -10.3 approximately -2.7%, respectively. The recovery of LSB from serum sample ranged from 73.2 to 79.5%, with that of HPC (internal standard) being 75.1 %. The lower limit of quantification for LSB was 10 ng/mL using 50 microL of serum sample.
    Archives of Pharmacal Research 01/2005; 27(12):1202-6. · 1.54 Impact Factor
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    ABSTRACT: A rapid, sensitive and selective hydrophilic interaction liquid chromatography-tandem mass spectrometric (HILIC-MS/MS) method for the determination of levosulpiride in human plasma was developed. Levosulpiride and internal standard, tiapride were extracted from human plasma with ethyl acetate at pH 11 and analyzed on an Atlantis HILIC silica column with the mobile phase of acetonitrile-ammonium formate (190 mM, pH 3.0) (94:6, v/v). The analytes were detected using an electrospray ionization tandem mass spectrometry in the multiple-reaction-monitoring mode. The standard curve was linear (r = 0.999) over the concentration range of 1.00-200 ng/ml. The lower limit of quantification for levosulpiride was 1.00 ng/ml using 100 microl plasma sample. The coefficient of variation and relative error for intra- and inter-assay at three quality control (QC) levels were 3.8-9.1 and -2.9 to -0.1%, respectively. The recoveries of levosulpiride ranged from 80.5 to 87.4%, with that of tiapride (internal standard) being 84.6%. This method was successfully applied to the pharmacokinetic study of levosulpiride in humans.
    Journal of Chromatography B 11/2004; 809(2):345-50. · 2.49 Impact Factor
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    ABSTRACT: A rapid, sensitive and selective hydrophilic interaction liquid chromatography-tandem mass spectrometric (HILIC-MS/MS) method for the determination of tiapride in human plasma was developed. Tiapride and internal standard, metoclopramide were extracted from human plasma with dichloromethane at basic pH and analyzed on an Atlantis HILIC silica column with the mobile phase of acetonitrile-ammonium formate (190 mM, pH 3.0) (94:6, v/v). The analytes were detected using an electrospray ionization tandem mass spectrometry in the multiple-reaction-monitoring mode. The standard curve was linear (r=0.999) over the concentration range of 1.00-200 ng/mL. The coefficient of variation and relative error for intra- and interassay at three QC levels were 6.4-8.8% and -2.0-3.6%, respectively. The recoveries of tiapride ranged from 96.3 to 97.4%, with that of metoclopramide (internal standard) being 94.2%. The lower limit of quantification for tiapride was 1.00 ng/mL using 100 microL of plasma sample.
    Archives of Pharmacal Research 10/2004; 27(9):901-5. · 1.54 Impact Factor