• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.402.3-403
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• 2002

Cilostazol. a quinolinone derivative that inhibits phosphodiesterase. is used for the treatment of intermittent claudication resulting from peripheral arterial disease. In order to perform pharmacological and pharmacokinetic studies of cilostazol, specific. sensitive and reproducible analysis methods are demanded. Therefore. in the present study. an analytical method of cilostazol in human plasma was developed using semi-microbore HPLC equipped with automated column switching system. (omitted)

• 약학회지
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• 제34권5호
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• pp.334-340
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• 1990

The bioequivalence of Mandol and Mancef (cefamondole nafate injection preparation) was investigated for 8 healthy human volunteers. Cefamandole nafate hydrolysis to cefamandole base in the blood and shows antibacterial activity. As the rate of the hydrolysis can be varied according to the buffer used in the preparation, the bioequivalence of cefamandole nafate I.V. was studied. A new HPLC method, the column switching technique, was developed and used for the simultaneous determination of cefamandole and cefamandole nafate in the plasma and in the urine. There were no statistically significant difference in between Mandol and Mancef for the parameters of AUC and Cp 0.25 hr even through the power of the test was not enough.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2006년도 추계학술대회
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• pp.65-74
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• 2006

Modem drug discovery requires rapid pharmacokinetic evaluation of chemically diverse compounds for early candidate selection. This demands the development of analytical methods that offer high-throughput of samples. Naturally, liquid chromatography / tandem mass spectrometry (LC-MS/MS) is choice of the analytical method because of its superior sensitivity and selectivity. As a result of the short analysis time(typically 3-5min) by LC-MS/MS, sample preparation has become the rate- determining step in the whole analytical cycle. Consequently tremendous efforts are being made to speed up and automate this step. In a typical automated 96-well SPE(solid-phase extraction) procedure, plasma samples are transferred to the 96-well SPE plate, internal standard and aqueous buffer solutions are added and then vacuum is applied using the robotic liquid handling system. It takes only 20-90 min to process 96 samples by automated SPE and the analyst is physically occupied for only approximately 10 min. Recently, the ultra-high flow rate liquid chromatography (turbulent-flow chromatography)has sparked a huge interest for rapid and direct quantitation of drugs in plasma. There is no sample preparation except for sample aliquotting, internal standard addition and centrifugation. This type of analysis is achieved by using a small diameter column with a large particle size(30-5O ${\mu}$m) and a high flow rate, typically between 3-5 ml/min. Silica-based monolithic HPLC columns contain a novel chromatographic support in which the traditional particulate packing has been replaced with a single, continuous network (monolith) of pcrous silica. The main advantage of such a network is decreased backpressure due to macropores (2 ${\mu}$m) throughout the network. This allows high flow rates, and hence fast analyses that are unattainable with traditional particulate columns. The reduction of particle diameter in HPLC results in increased column efficiency. use of small particles (<2 urn), however, requires p.essu.es beyond the traditional 6,000 psi of conventional pumping devices. Instrumental development in recent years has resulted in pumping devices capable of handling the requirements of columns packed with small particles. The staggered parallel HPLC system consists of four fully independent binary HPLC pumps, a modified auto sampler, and a series of switching and selector valves all controlled by a single computer program. The system improves sample throughput without sacrificing chromatographic separation or data quality. Sample throughput can be increased nearly four-fold without requiring significant changes in current analytical procedures. The process of Bioanalytical Method Validation is required by the FDA to assess and verify the performance of a chronlatographic method prior to its application in sample analysis. The validation should address the selectivity, linearity, accuracy, precision and stability of the method. This presentation will provide all overview of the work required to accomplish a full validation and show how a chromatographic method is suitable for toxirokinetic sample analysis. A liquid chromatography/tandem mass spectrometry (LC-MS/MS) method developed to quantitate drug levels in dog plasma will be used as an example of tile process.

• Journal of Pharmaceutical Investigation
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• 제33권4호
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• pp.311-317
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• 2003

Felodipine is a calcium antagonist that lowers blood pressure by reducing peripheral resistance by meas of a direct, selective action on smooth muscle in arterial resistance vessels. Futhermore, it have been approved for the effective in angina pectoris and cardiac failure. The purpose of the present study was to evaluate the bioequivalence of two felodipine extended release (ER) tablets, Splendil (YuHan Corporation) and Stapin (Hana Pharmaceutial Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). The felodipine release from the two felodipine formulations in vitro was tested using KP VIII Apparatus II method at pH 6.5 buffer solution. Twenty six healthy male subjects, $22.73{\pm}1.78$ years in age and $66.66{\pm}7.28\;kg$ in body weight, were divided into two groups and a radomized $2{\times}2$ cross-over study was employed. After two tablets containing 5 mg as felodipine were orally administered, blood sample was taken at predetermined time intervals and the concentrations of felodipine in serum were determined using column-switching HPLC method with UV detector. The dissolution profiles of two formulations were similar at pH 6.5 buffer solution. Besides, the 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 $AUC_t\;and\;C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the Splendil were 2.53%, 1.32% and 18.32% for $AUC_t,\;C_{max}\;and\;T_{max}$, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance rage of log(0.86) to log(1.25) $(e.g.,\;log(0.86){\sim}log(1.20)\;and\;log(0.89){\sim}log(1.23)\;for\;AUC_t,\;C_{max},\;respectively)$. Thus, the criteria of the KFDA guidelines for the bioequivalence was satisfied, indicating Stapin ER tablet and Splendil ER tablet are bioequivalent.

• Journal of Pharmaceutical Investigation
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• 제41권2호
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• pp.117-123
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• 2011

Loxoprofen sodium, a 2-phenylpropionate non-steroidal anti-inflammatory drug (NSAID), has marked analgesic and antipyretic activities and relatively weak gastrointestinal ulcerogenicity. The purpose of the present study was to evaluate the bioequivalence of two loxoprofen sodium tablets, Hana loxoprofen sodium tablet (Hana Pharm. Co., Ltd.) and Dongwha Loxonin$^{(R)}$ tablet (Dongwha Pharm. Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The in vitro release of loxoprofen from the two loxoprofen sodium formulations was tested using KP IX Apparatus II method with various dissolution media. Twenty four healthy Korean male volunteers, $22.83{\pm}1.862$ years in age and $69.92{\pm}9.14$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ crossover study was employed. After a single tablet containing 60 mg as loxoprofen sodium was orally administered, blood samples were taken at predetermined time intervals and the concentrations of loxoprofen in serum were determined using a online column-switching HPLC method with UV/Vis detection. The dissolution profiles of two formulations were similar in all tested dissolution media. The pharmacokinetic parameters such as $AUC^t$, $C_{max}$ and $T_{max}$ were calculated, and computer programs (Equiv Test and K-BE Test 2002) were utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t$, $C_{max}$ and un-transformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug, Dongwha Loxonin$^{(R)}$ tablet, were 2.03, 2.99 and -9.49% for $AUC_t$, $C_{max}$, and $T_{max}$, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log0.8 to log1.25 (e.g., log0.9831~log1.0535 and log0.9455~log1.1386 for $AUC_t$ and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Hana loxoprofen sodium tablet was bioequivalent to Dongwha Loxonin$^{(R)}$ tablet.

• 한국임상약학회지
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• 제20권3호
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• pp.235-241
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• 2010

Bambuterol hydrochloride, dimethylcarbamic acid 5-[2-(1,1-dimethylethyl)amino-1-hydroxyethyl]-1,3-phenylene ester hydrochloride, is the prodrug of active ${\beta}_2$-adrenergic metabolite terbutaline. The purpose of the present study was to evaluate the bioequivalence of two bambuterol hydrochloride tablets, $Bambec^{(R)}$ tablet 10 mg (Yuhan Co., Ltd.) and Bambucol tablet 10 mg (Sam Chun Dang Pharm. Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). In vitro release of bambuterol from two bambuterol hydrochloride formulations was tested using KP VIII Apparatus II method with various dissolution media. Twenty eight healthy male Korean volunteers, $23.86{\pm}1.65$ years in age and $68.98{\pm}9.58$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After two tablets containing 10 mg as bambuterol hydrochloride were orally administered, blood samples were taken at predetermined time intervals, and the concentrations of bambuterol in serum were determined using column switching HPLC with UV detector. The dissolution profiles of two formulations were similar in all tested dissolution media. The pharmacokinetic parameters such as $AUC_t$, $C_{max}$ and $T_{max}$ were calculated, and ANOVA test with K-BE Test 2002 was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t$, $C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug, $Bambec^{(R)}$, were -8.10%, -3.82% and 12.65% for $AUC_t$, $C_{max}$ and $T_{max}$, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log 0.8 to log 1.25 (i.e., log 0.8093~log 1.0302 and log 0.8564~log 1.1280 for $AUC_t$ and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Bambucol tablet 10 mg was bioequivalent to $Bambec^{(R)}$ tablet 10 mg.

• Toxicological Research
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• 제20권3호
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• pp.195-203
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• 2004

4-Tert-Octylphenol (OP) is a surfactant additive widely used in the manufacture of a variety of detergents and plastic products. OP can disrupt endocrine function in humans and animals. This study was carried out to obtain toxicokinetic parameters of OP in male Sprague-Dawley (SD) rats. Male rats were administered with OP by single oral application of 200 mg/kg body weight. Blood, urine and tissues samples were taken at several time intervals after administration. Analysis of samples for OP was performed by column-switching high performance liquid chromatography (HPLC). In addition, we exam-ined tissue distribution and accumulation of OP after single oral application of 50, 100, and 200 mg/kg, single intravenous injection of 1, 5 and 10 mg/kg or daily application of 50 mg/kg for 14 consecutive days. After single oral administration of 200 mg/kg, Cmax of 213 $\pm$ 123 ng/ml was reached within the first 1.3 hr (Tmax) in the plasma. AUC was calculated for 1,333$\pm$484 ngㆍhr/ml. The final elimination half-life of plasma was longer than that of urine, but urinary clearance was lower than oral. A very small fraction of OP (Fe < 0.0017%) was excreted in urine within 24 hr. These results indicated that the major excretion route of OP was not urine. The mean maximal tissue distribution of OP was obserbed at 6 hr after treatment and slowly decreased time-dependently. High OP concentrations were detected in fat at 24 hr. The OP in fat was slowly released with longer elimination half-life and lower clearance than that of other tissues. OP was not accumulated in the liver following single oral application but 14-day oral treatments resulted in two-fold accumulation. It was probably due to the saturation of detoxification pathways. On the other hand, the mRNA expression of cytochrome P450 isoforms except CYP2C11 was not affected by OP at any dose. The expression of CYP2C11 mRNA decreased in a dose-dependent manner. This result suggests that OP changes expression of the male-specific cytochrome P450 isoforms in rat liver, and these changes are closely related to the toxic and estrogenic effect of OP.

• Food Science and Biotechnology
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• 제17권2호
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• pp.262-266
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• 2008

This study was conducted to provide a vitamin $B_{12}$ database for the representative Korean food items and to assess the dietary intake assessment of vitamin $B_{12}$ for Koreans. The vitamin $B_{12}$ content of 106 foods had been determined by high performance liquid chromatography (HPLC) using column switching method. Rich sources of vitamin $B_{12}$ were meats, milk, and egg ($0.3-3.4\;{\mu}g/100g$). Vegetables and fruits contained vitamin $B_{12}$ below limit of detection (LOD). The major food sources for vitamin $B_{12}$ intake were milk (72.0%), meats (22.3%), egg (3.6%), and fishes & shellfishes (2.1%). Mean vitamin $B_{12}$ intake of Koreans was $3.16\;{\mu}g$/person/day. The proportion of population with intake below estimate average requirement (EAR) and above recommended intake (RI) of vitamin $B_{12}$ was 60.7 and 36.5%, respectively. The vitamin $B_{12}$ intake level of young children with 1-2 years which was 834.6% of RI while the intake level of the older adults 50 years and older was only 70.0% of RI. Also, there were regional differences between urban and rural area. The population with intake below RI was larger than that with intake above RI in Korea.

• Biomolecules & Therapeutics
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• 제16권3호
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• pp.255-260
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• 2008

The purpose of this study was to evaluate the bioequivalence of the test (Daewoo Hydrocortisone 10 mg, Daewoo Pharm. Co., Busan, Korea) and reference (Jenapharm Hydrocortisone 10 mg, JayTech Biogen, Seoul, Korea) hydrocortisone tablets. Twenty-four healthy male Korean volunteers were divided into two groups with a randomized $2{\times}2$ cross-over design. In order to suppress the endogenous cortisol secretion, a single oral dose of Dexamethasone (4 mg) was administered 10 hr prior to hydrocortisone administration. Blood samples were withdrawn for 10 hr at the predetermined intervals after a single oral dose of hydrocortisone (20 mg). The serum concentration of hydrocortisone was analyzed by HPLC/UV using a column switching method after liquid-liquid extraction process. The pharmacokinetic parameters ($AUC_{0{\sim}10hr}$, $C_{max}$, and $T_{max}$) of the test and reference hydrocortisone tablets were determined while the secretion of endogenous cortisol was being suppressed. The pharmacokinetic parameters of the test tablet were not statistically different from those of the reference tablet at ex value was 0.05. The 90% confidence intervals for the average ratio (test/reference) of $AUC_{0{\sim}10hr}$ and $C_{max}$ were within the Korea Food and Drug Administration acceptance range of 0.80-1.25 ($0.89{\sim}0.99$ and $0.86{\sim}0.99$ for $AUC_{0{\sim}10hr}$ and $C_{max}$, respectively). Therefore it was concluded that the test tablet, Daewoo Hydrocortisone tablet was bioequivalent to the reference tablet, Jenapharm Hydrocortisone tablet.

• KSBB Journal
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• 제23권2호
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• pp.135-141
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• 2008

SMB 크로마토그래피를 위한 예비 실험으로서 L-ribose와 L-arabinose의 혼합물의 분리 특성을 $NH_2$ 컬럼을 사용하여 확인하였고 두 성분 분리 최적 조건으로 Acetonitrile과 증류수의 조성이 85/15 (v/v)에서 실험을 수행하였다. PIM(Pulse input method)과 Aspen chromatography 전산모사를 통해 L-ribose와 L-arabinose가 선형 흡착등온식을 따르는 것을 알 수 있었으며 각 성분의 Henry상수를 추산하였고 다음과 같다. $$C_{S,Ribose}=3.51{\cdot}C_{M.Ribose}$$ $$C_{S,Arabinose}=5.07{\cdot}C_{M.Arabinose}$$ 이를 바탕으로 SMB 크로마토그래피의 최적 운전조건을 수립하기 위하여 Triangle 이론에 의한 운전 조작변수를 추산함으로서 $m_2\;=\;3.51$, $m_3\;=\;5.07$일 때 즉, 삼각형에서 꼭지점의 조건에서 L-ribose와 L-arabinose의 순도가 각각 85, 80% 정도로 두 성분의 분리에 있어서 가장 효과적인 운전 조건임을 확인 할 수 있었다.