• Journal of Pharmaceutical Investigation
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• 제35권3호
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• pp.187-192
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• 2005

The purpose of the present study was designed to evaluate the bioequivalence of two benidipine hydrochloride tablets, Codipine (Youngjin Pharm. Co., Ltd.) and Benipine (Myungmoon Pharm. Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty-four normal male volunteers, $23.00{\pm}1.82$ year in age and $70.08{\pm}9.59$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After two tablets containing 4 mg of benidipine hydrochloride were orally administered, blood was taken at predetermined time intervals and concentrations of benidipine in plasma were determined using LC-MS/MS. Pharmacokinetic parameters such as $AUC_t$, $C_{max}$ and $T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t$, and $C_{max}$. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals for the log transformed data were acceptance range of log0.8 to log1.25 $(e.g., \;log1.04{\sim}log1.24\;and\;log0.91{\sim}log1.09$ for $AUC_t$, and $C_{max}$ respectively). The major parameters, $AUC_t$ and $C_{max}$, met the criteria of KDFA for bioequivalence indicating that Benipine tablet is bioequivalent to Codipine tablet.

• 분석과학
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• 제13권3호
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• pp.385-393
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• 2000

뇨시료 중 amineptine의 (dihydro-10, 11-dibenzo[a, d] cycloheptenyl-5-amino-7-heptanoic acid) metabolites를 분석하기 위한 최적조건을 찾기 위하여 pH 변화에 따른 추출률과 세가지의 유도체화시약에 대한 반응성을 조사해본 결과 pH는 9.5, 유도체화시약은 carboxylic acid group에 MSTFA로 반응 시켰을 경우 좋은 결과를 나타내었다. GC/MS를 이용하여 amineptine을 복용한 사람의 뇨를 분석한 결과 amineptine과 그 대사물질인 dihydro-10, 11-dibenzo[a, d] cycloheptenyl-5-amino-5-pentanoic acid ($C_5$-metabolite)와 $C_5$-metabolite의 lactamized product인 ${\delta}$-lactam을 확인하였다. Amineptine과 그 metabolite들을 GC/MS-SIM mode로 분석하기 위한 monitoring ion들은 m/z 192를 공통 이온으로 선정하였으며, 각각의 분자이온을 선정하였다. Amineptine의 excretion study 결과, amineptine, ${\delta}$-lactam 및 $C_5$-metabolite는 4시간이내에 70-90%가 배설되었고 20시간 이내에 거의 배설이 완결되었다.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1998년도 Proceedings of UNESCO-internetwork Cooperative Regional Seminar and Workshop on Bioassay Guided Isolation of Bioactive Substances from Natural Products and Microbial Products
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• pp.143-143
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• 1998

Antagonists acting at the glycine site of the NMDA receptor have been gaining safer alternatives for stroke therapy because they have few adverse effect competitive and noncompetitive NMDA antagonists. Therefore, the neuroprotect novel glycine site antagonist KC0244 were evaluated in a rat model of transient comparison with GV150526A in a developmental phase. Middle cerebral artery oc was produced by insertion of a silicone-coated 4-0 nylon monofilament to the o in male Sprague-Dawley rats under isoflurane anesthesia. After 90 or 120 min retracted and the ischemic tissue reperfused. In 90-min MCAO model, GV150526A was administered 30 min before MCAO or immediately after MCAO. In 120-min MC KC0244 or GV150526A (10 mg/kg, i.p.) was administered 1 hr before MCAO or imme MCAO. Infarct volume was measured 24 hr after MCAO using the 2,3,5-triphe chloride staining method. In 90-min MCAO model, treatments with GV1505 significantly reduce infarct volume although they tended to slightly reduce cor approximately 19% compared with the nontreated group. In 120-min MCAO model with GV150526A did not either significantly reduce infarct volume although the reduce total infarct volume by approximately 16% compared with the vehicle-tre However, 1-hr preischemic and immediate treatments with KC0244 reduced total i 39 and 30% (corrected total infarct volume by 44 and 32%), respectively, co vehicle-treated control group. The results suggest that KC0244 can provid against transient focal ischemic damage with greater in vivo potency than GV150

• Journal of Pharmaceutical Investigation
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• 제39권5호
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• pp.321-325
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• 2009

5-HT$_{2C}$ receptors have been considered as therapeutic targets for the treatment of various central nervous system disorders such as depression, anxiety, epilepsy, schizophrenia and sleep disorders. We chemically synthesized KKHQ80114 (K14) and KKHQ80109 (K09), selective 5-HT$_{2C}$ agonists, with the purpose of developing therapeutic agents for the treatment of obesity. The objective of this work is to investigate analytical methods of these compounds in the plasma and urine of rats by gas chromatography/mass spectrometry. In this experiment, K14 was determined in plasma and urine by using K09 as internal standard. Calibration curves give a good linearity in plasma (r$^2$=0.9993) and urine (r$^2$=0.9988). Among hexane, ethyl acetate and diethyl ether, the highest peak was observed in diethyl ether. However, ethyl acetate was used since more interfering peaks were observed with diethyl ether. Inter-day precision and accuracy were determined in the ranges of 50-500 ng/mL for plasma and 10-500 ng/ml for urine. Quantitation limits were 50 ng/mL plasma and 25 ng/ mL urine. These data may be applicable for further studies of these compounds including absorption and metabolism due to no pharmacokinetic or analytical data available.

• Journal of Pharmaceutical Investigation
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• 제39권5호
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• pp.327-331
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• 2009

5-HT$_{2C}$ receptors have been considered as therapeutic targets for the treatment of various central nervous system disorders such as depression, anxiety, epilepsy, schizophrenia and sleep disorders. We chemically synthesized KKHQ80109 (K09) and KKHQ80114 (K14), selective 5-HT$_{2C}$ agonists, with the purpose of developing therapeutic agents for the treatment of obesity. The objective of this work is to investigate pharmacokinetic parameters and bioavailability of K09 and K14 in rats given orally or intravenously. Oral administration of 20 mg/kg K09 results in 4.11 hr of the terminal half-life and 89.16 ng/mL of C$_{max}$ at 5.00 hr (T$_{max}$). The terminal half-life of K14 was 3.83 hr with 215.81 ng/mL of C$_{max}$ at 3.33 hr (T$_{max}$) after oral dosing of 20 mg/kg K14, indicating that K14 is more rapidly absorbed than K09. Bioavailability showed 0.17-0.21 for K09 and 0.19-0.23 for K14. Urinary excretion of parent K09 and K14 was less than 1%, indicating that K09 and K14 undergo very extensive hepatic metabolism.

• Bulletin of the Korean Chemical Society
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• 제24권1호
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• pp.65-69
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• 2003

The kinetic and chemical mechanisms of AChE-catalyzed hydrolysis of short-chain thiocholine esters are relatively well documented. Up to propanoylthiocholine (PrTCh) the chemical mechanism is general acid-base catalysis by the active site catalytic triad. The chemical mechanism for the enzyme-catalyzed butyrylthiocholine(BuTCh) hydrolysis shifts to a parallel mechanism in which general base catalysis by E199 of direct water attack to the carbonyl carbon of the substrate. [Selwood, T., et al. J. Am. Chem. Soc. 1993, 115, 10477- 10482] The long chain thiocholine esters such as hexanoylthiocholine (HexTCh), heptanoylthiocholine (HepTCh), and octanoylthiocholine (OcTCh) are hydrolyzed by electric eel acetylcholinesterase (AChE). The kinetic parameters are determined to show that these compounds have a lower Michaelis constant than BuTCh and the pH-rate profile showed that the mechanism is similar to that of BuTCh hydrolysis. The solvent isotope effect and proton inventory of AChE-catalyzed hydrolysis of HexTCh showed that one proton transfer is involved in the transition state of the acylation stage. The relationship between the dipole moment and the Michaelis constant of the long chain thiocholine esters showed that the dipole moment is the most important factor for the binding of a substrate to the enzyme active site.

• Journal of Biomedical and Translational Research
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• 제19권4호
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• pp.130-139
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• 2018

This study aimed to analyze a high-performance liquid chromatography (HPLC) separation using a pentafluorophenyl column of parent drug hydroxychloroquine (HCQ) and its active metabolite, desethylhydroxchloroquine (DHCQ) applying to determine bioequivalence of two different formulations administered to patients. A rapid, simple, sensitive and specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated for bioanalysis of HCQ and its metabolite DHCQ in human whole blood using deuterium derivative $hydroxychloroquine-D_4$ as an internal standard (IS). A triple-quadrupole mass spectrometer was operated using electrospray ionization in multiple reaction monitoring (MRM) mode. Sample preparation involves a two-step precipitation of protein techniques. The removed protein blood samples were chromatographed on a pentafluorophenyl (PFP) column ($50mm{\times}4.6mm$, $2.6{\mu}m$) with a mobile phase (ammonium formate solution containing dilute formic acid) in an isocratic mode at a flow rate of 0.45 mL/min. The standard curves were found to be linear in the range of 2 - 500 ng/mL for HCQ; 2 - 2,000 ng/mL for DHCQ in spite of lacking a highly sensitive MS spectrometry system. Results of intra- and inter-day precision and accuracy were within acceptable limits. A run time of 2.2 min for HCQ and 2.03 min for DHCQ in blood sample facilitated the analysis of more than 300 human whole blood samples per day. Taken together, we concluded that the assay developed herein represents a highly qualified technology for the quantification of HCQ in human whole blood for a parallel design bioequivalence study in a healthy male.

• Bulletin of the Korean Chemical Society
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• 제33권2호
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• pp.549-552
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• 2012

This report presents a mobile instrumentation platform based on a smartphone using its built-in functions for colorimetric diagnosis. The color change as a result of detection is taken as a picture through a CCD camera built in the smartphone, and is evaluated in the form of the hue value to give the well-defined relationship between the color and the concentration. To prove the concept in the present work, proton concentration measurements were conducted on pH paper coupled with a smartphone for demonstration. This report is believed to show the possibility of adapting a smartphone to a mobile analytical transducer, and more applications for bioanalysis are expected to be developed using other built-in functions of the smartphone.

• Mass Spectrometry Letters
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• 제6권2호
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• pp.31-37
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• 2015

Phosphorylation upon protein is well known to a key regulator that implicates in modulating many cellular processes like growth, migration, and differentiation. Up to date, grafting of multidimensional separation techniques onto advanced mass spectrometry (MS) has emerged as a promising tool for figuring out the biological functions of phosphorylation in a cell. However, advanced MS-based phosphoproteomics is still challenging, due to its intrinsic issues, i.e., low stoichiometry, less susceptibility in positive ion mode, and low abundance in biological sample. To overcome these bottlenecks, diverse techniques (e.g., SCX, HILIC, ERLIC, IMAC, TiO₂, etc.) are continuously developed for on-/off-line enrichment of phosphorylated protein (or peptide) from biological samples, thereby helping qualitative/quantitative determination of phosphorylated protein and its phosphorylated sites. In this review, we introduce to the overall views of enrichment tools that are universally used to selectively isolate targeted phosphorylated protein (or peptide) from ordinary ones before MS-based phospoproteomic analysis.

• Archives of Pharmacal Research
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• 제29권9호
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• pp.741-745
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• 2006

In our efforts to discover novel phytoestrogens to treat menopausal symptoms, eleven furanocoumarins were isolated from Angelica dahurica and tested for their estrogenic activity on the Ishikawa cell line. Among the compounds tested, 9-hydroxy-4-methoxypsoralen and alloisoimperatorin showed strong abilities to induce alkaline phosphatase (AP) with $EC_{50}$ values of 1.1 and $0.8\;{\mu}g/mL$, respectively, whereas the other nine furanocoumarins were weakly or only slightly active.