• Analytical Science and Technology
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• v.17 no.2
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• pp.117-129
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• 2004

Amitrole in environment, difficult to be analyzed by GC or GC/MS due to high polarity and low volatility, was analyzed by LC/ESI/MS in the study. Maximum peak intensity of amitrole in LC/MS/ESI mass spectrum is m/z 85 of protonated molecular ion $(M+H)^+$ with 30V of cone voltage at SIR mode. It was confirmed that ratios between main ion of amitrole, 85 of protonated molecular ion, and m/z 58 fragmented ion of amitrole, had increased corresponding with the increment of cone voltage from 20V to 70V. The isotope molecular weight of amitrole was $86([M+H])^+$ at LC/MS analysis and the mass spectrum ratio between 85 mass and 86 mass was not different by the change of concentration but similar to theoretical ratio(less than 10% standard deviation).The linearity of standard calibration curve under same condition with sample treatment method had $y=1.09354e^6X+26947.2$ and $r^2=0.99$. Recovery rates in water and soil samples were 77.64~83.44% and 71.11~79.44%, respectively. Reliability of the analysis was performed with 5 repeated measurements at each level of standard concentration and the result showed that relative standard deviation was less than 10%; therefore, the extraction and analysis method in the study suggested that it would be reliable to measure amitrole in water and soil media.

• YAKHAK HOEJI
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• v.49 no.3
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• pp.212-216
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• 2005

A rapid, sensitive and selective electrospray tandem mass spectrometric (ESI-LC/MS/MS) method for the quantitation of gliquidone in human plasma was developed. A bioavailability study of gliquidone tablet (30 mg gliquidone, Boehringer Ingelheim Korea Co.) was performed using the validated ESI-LC/MS/MS method. The dose of 30 mg of gliquidone (1 tablet) was orally administered to 9 healthy Korean subjects. After administration, blood was taken at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 7, 9, 12, 24, and 33 hour. The validation data were as follows; the standard curve was linear ($r^2$=0.999) over the concentration range of $10\~1000 ng/ml$. The coefficient of variation for intra- and inter-day assay were $8.30\~18.86$, and $2.19\~12.92\%$, respectively. The lower limit of quantification for gliquidone was 10 ng/ml. The pharmacokinetic parameters obtained were as follows; $AUC_t$ was 3861.17$\pm$1328.61 ng-hr/ml, $C_{max}$ was 831.02$\pm$227.99 ng/ml, $T_{max}$ was $2.94{\pm}0.77 hr,\;K_e$, was 0.19$\pm$0.06 1/hr, and $t_{l/2}$ was 4.47$\pm$3.52 hr. Based on the validated analytical method and pharmacokinetic parameters, a standard guideline of the bioavailability test of gliquidone dosage forms was prepared successfully and could be used for the bioequivalence test of gliquidone preparation.

• YAKHAK HOEJI
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• v.49 no.3
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• pp.225-229
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• 2005

A rapid, sensitive and selective tandem mass spectrometric method (LC-MS/MS) for the quantitation of nicorandil in human plasma was developed. A bioavailability study of Sigmat tablet (5 mg nicorandil, Choongwae Co.) was per-formed using the validated LC-MS/MS method. The dose of 5 fig of nicorandil (1 tablet) was orally administered to 9 healthy Korean subjects. After administration, blood was taken at 0.25, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, and 24 hour. The validation data were as follows; the standard curve was linear ($r^2$=0.999) over the concentration range of $0.5\~200.0 ng/ml$. The coefficient of variation for intra- and inter-day assay were $3.55\~7.44$, and $2.17\~9.102\%$, respectively. The lower limit of quantification for nicorandil was 0.5 ng/ml. The pharmacokinetic parameters obtained were as follows; $AUC_t$ was 145.9$\pm$83.0 ng-hr/ml, Cmax was 83.8$\pm$32.2 ng/ml, $C_{max}$ was 0.42$\pm$0.13 hr, $K_e$ was 0.56$\pm$0.23 l/hr, and $t_{l/2}$ was 1.42$\pm$0.52 hr. Based on the validated analytical method and pharmacokinetic parameters, a standard guideline of the bioavailability test of nicorandil dos-age forms was prepared successfully and could be used for the bioequivalence test of nicorandil preparation.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.174.3-175
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• 2003

1-and 2-Bromopropane were reported as the causative agents for reproductive toxicity and immunotoxicity. The glutathione (GSH) metabolites resulting from in vitro treatment of 1- and 2-bromopropane were detected, identified and characterized. For the facile identification, expected GSH metabolites rormed by 1- and 2-bromopropane were chemically synthesized as reference materials (positive controls) and characterized by $^1H$-NMR, $^13C$-NMR, HPLC and LC/MS/MS. The treatment of GSH and S-9 fraction with 1- or 2-bromopropane at a physiological condition (pH 7.4, $37^\times$) for 1hr produced GSH metabolites, which were identified by UV, HPLC and ESI LC/MS/MS analyses. (omitted)

• Proceedings of the Korean Society of Near Infrared Spectroscopy Conference
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• 2001.06a
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• pp.3114-3114
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• 2001

During the last years phytochemistry and phytopharmaceutical applications have developed rapidly and so there exists a high demand for faster and more efficient analysis techniques. Therefore we have established a near infrared transflectance spectroscopy (NIRS) method that allows a qualitative and quantitative determination of new polyphenolic pharmacological active leading compounds within a few seconds. As the NIR spectrometer has to be calibrated the compound of interest has at first to be characterized by using one or other a combination of chromatographic or electrophoretic separation techniques such as thin layer chromatography (TLC), high performance liquid chromatography (HPLC), capillary electrophoresis (CE), gas chromatography (GC) and capillary electrochromatography (CEC). Both structural elucidation and quantitative analysis of the phenolic compound is possible by direct coupling of the mentioned separation methods with a mass spectrometer (GC-MS, LC-MS/MS, CE-MS, CEC-MS) and a NMR spectrometer (LC-NMR). Furthermore the compound has to be isolated (NPLC, MPLC, prep. TLC, prep. HPLC) and its structure elucidated by spectroscopic techniques (UV, IR, HR-MS, NMR) and chemical synthesis. After that HPLC can be used to provide the reference data for the calibration step of the near infrared spectrometer. The NIRS calibration step is time consuming, which is compensated by short analysis times. After validation of the established NIRS method it is possible to determine the polyphenolic compound within seconds which allows to raise the efficiency in quality control and to reduce costs especially in the phytopharmaceutical industry.

• Journal of Pharmaceutical Investigation
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• v.36 no.6
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• pp.413-419
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• 2006

In this study, the main purpose was to evaluate the bioequivalence of two thioctic acid tablests, Thioctacid HR tablet(Bukwang Pharm. Co., Ltd.) and Daewon thioctic acid HR tablet 600 mg(Daewon Pharm. Co., Ltd.), according to the guidelines of Korea Food and Drug Administration(KFDA). Twenty-four, healthy Korean volunteers were divided into two groups, randomized and treated by $2{\times}2$ crossover study. After the administration of one thioctic acid tablet containing 600 mg thioctic acid, blood samples were taken until 8 hr after the oral administration. LC-MS/MS was applied to determination of thioctic acid, and we calculated the $AUC_t,\;C_{max},\;T_{max}$ from the plasma concentration-time data. Analysis of variance(ANOVA) was carried out using logarithmically transformed $AUC_t\;and\;C_{max}$. No significant sequence effect was found for all of the bioavailability parameters indicating that the crossover design was properly performed. The 90% confidence intervals of the $AUC_t$ ratio and the $C_{max}$ ratio for Daewon thioctic acid tablet 600 mg/Thioctacid HR were log 0.9877$\sim$log 1.1938 and log 0.8169$\sim$log 1.2237, respectively. These values were within the acceptable bioequivalence intervals of log 0.80$\sim$log 1.25, recommended by KFDA. In all of these results we concluded that Daewon thioctic acid tablet 600 mg was bioequivalent to Thioctacid HR tablet, in terms of rate and extent of absorption.

• Mass Spectrometry Letters
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• v.12 no.4
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• pp.172-178
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• 2021

HYIpro-3-1 is an adjuvant for preventing or treating inflammatory growth diseases. In this study, we identified the metabolic pathway of HYIpro-3-1 in human liver microsomes (HLMs) by quadrupole-orbitrap high-resolution mass spectrometry (HR-MS) and characterized the major human cytochrome P450 (CYP). Ten metabolites were identified, including one O-demethylation (M1), two O-demethylation and monohydroxylation (M2 and M3), and seven monohydroxylation metabolites (M4-M10). Based on the HR-MS² spectra, the metabolites are divided into two groups of monohydroxylated metabolites according to the hydroxylation position. We verified that HYIpro-3-1 is metabolized by CYP in HLMs, CYP2B6 is mainly involved in O-demethylation, and various CYPs are involved in the monohydroxylation of HYIpro-3-1.

• Journal of Pharmaceutical Investigation
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• v.38 no.4
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• pp.277-282
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• 2008

The purpose of the present study was to evaluate the bioequivalence of two topiramate tablets, Topamax tablet (Janssen Korea. Co., Ltd., Seoul, Korea, reference drug) and Topamin tablet (Myungmoon Pharm. Co., Ltd., Seoul, Korea, test drug), according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty-four healthy male Korean volunteers received one tablet at the dose of 100 mg topiramate in a $2{\times}2$ crossover study. There were two-weeks washout period between the doses. Plasma concentrations of topiramate were monitored by an LC-MS/MS for over a period of 96 hr after administration. $AUC_t$ (the area under the plasma concentration-time curve from time zero to 96 hr) was calculated by the linear trapezoidal rule method. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were compiled from the plasma concentration-time data. Analysis of variance (ANOVA) was carried out using logarithmically transformed $AUC_t$ and $C_{max}$. The 90% confidence intervals of the $AUC_t$, ratio and the $C_{max}$ ratio for Topamin/Topamax were $\log0.88{\sim}\log1.02$ and $\log0.87{\sim}\log1.03$, respectively. These values were within the acceptable bioequivalence intervals of $\log0.80{\sim}\log1.25$. Taken together, our study demonstrated the bioequivalence of Topamax and Topamin with respect to the rate and extent of absorption.

• Journal of Pharmaceutical Investigation
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• v.35 no.4
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• pp.287-293
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• 2005

The purpose of the present study was to evaluate the bioequivalence of two glimepiride tablets, Amaryl tablet (Handok & Aventis Korea, reference drug) and Mepiril tablet (Myungmoon Pharm. Co., Ltd., Korea, test drug), according to the guidelines of Korea Food and Drug Administration (KFDA). After adding an internal standard (glibenclamide) to human plasma, plasma samples were extracted using 1mL of methyl tertiary butyl ether. Compounds extracted were analyzed by reverse-phase HPLC with multiple reaction monitoring (MRM) mode analyte detection. This method for determination glimepiride proved accurate and reproducible, with a limit of quantitation of 2 ng/mL in human plasma. Twenty-four healthy male Korean volunteers received each medicine at the glimepiride dose of 2 mg in a $2{\times}2$ crossover study. There was a one-week washout period between the doses. Plasma concentrations of glimepiride were monitored by a LC-MS/MS for over a period of 12 hr after the administration. $AUC_t$ (the area under the plasma concentration-time curve from time zero to 12 hr) was calculated by the linear trapezoidal rule method. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed $AUC_t$ and $C_{max}$. No significant sequence effect was found for all of the bioavailability parameters indicating that the crossover design was properly performed. The 90% confidence intervals of the $AUC_t$ ratio and the $C_{max}$ ratio for Amaryl/Mepiril were log 0.9583-log 1.1357 and log 1.0570-log 1.2376, respectively. These values were within the acceptable bioequivalence intervals of log 0.80-log 1.25. Taken together, our study demonstrated the bioequivalence of Amaryl and Mepiril with respect to the rate and extent of absorption.

• Journal of Pharmaceutical Investigation
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• v.37 no.1
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• pp.57-62
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• 2007

The purpose of the present study was to evaluate the bioequivalence of two donepezil tablets, $Aricept^{TM}$ tablet (Dae Woong Pharm. Co., Ltd., Korea, reference drug) and $Donpezil^{TM}$ tablet (Dong Wha Pharm. Ind. Co., Ltd., Korea, test drug), according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty-four healthy male Korean volunteers received one tablet containing donepezil hydorchloride 10 mg in a $2{\times}2$ crossover study. There was a three-week washout period between the doses. Plasma concentrations of donepezil were monitored by an LC-MS/MS far over a period of 240 hr after the administration. $AUC_t$, (the area under the plasma concentration-time curve from time zero to 240 hr) was calculated by the linear trapezoidal rule method. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$)were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed $AUC_t$ and $C_{max}$, No significant sequence effects were found for all of the bioavailability parameters indicating that the crossover design was properly performed. The 90% confidence intervals of the $AUC_t$ and $C_{max}$ were log 0.95${\sim}$log 1.03 and log 0.94${\sim}$log 1.08, respectively. These values were within the acceptable bioequivalence intervals of log 0.80${\sim}$log 1.25. Taken together, our study demonstrated the bioequivalence of $Aricept^{TM}$ and $Donpezil^{TM}$ with respect to the rate and extent of absorption.