• Journal of Pharmaceutical Investigation
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• 제41권4호
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• pp.255-262
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• 2011

Method using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was developed and validated for the determination of pregabalin in plasma samples. Acquisition was performed by monitoring the transitions: m/z 160.1${\rightarrow}$142.2 for pregabalin and m/z 423.2${\rightarrow}$207.1 for losartan (as an internal standard). After cold acetonitrileinduced protein precipitation of the plasma samples, separation was performed with C18 column by isocratic mobile phase consisted of 10 mM ammonium acetate and acetonitrile (15:85, v/v). Results were linear over the concentration ranged from 0.1 to $10{\mu}g$/mL and the correlation coefficients (r) were $\geq0.99$. Intra- and inter-day precisions were $\leq6.02$ and $\leq11.04%$, respectively, and intra- and inter-day accuracies were 96.60-101.09 and 98.10-102.60%, respectively. This validated method was successfully applied to a bioequivalence study of two formulations of pregabalin, Daewoong pregabalin capsule (Daewoong Pharm. Co., Ltd.) and Lyrica$^{(R)}$ capsule (Pfizer Korea Ltd.) in twenty eight healthy Korean volunteers. The subjects received a single oral dose of each formulation (150 mg as pregabalin) in a randomized $2{\times}2$ crossover study and plasma samples were obtained from each subject at predetermined time intervals. Then, the pharmacokinetic parameters ($AUC_{0-t}$, $C_{max}$ and $T_{max}$) were calculated and statistically analyzed to assess the differences between two formulations. The 90% confidence intervals for the log-transformed data were acceptable range of log 0.8-log 1.25 (e.g., log 1.0048-log 1.0692 for AUC0-t, log 0.9142-log 1.0421 for $C_{max}$). Thus, $AUC_{0-t}$ and $C_{max}$ met the criteria of the Korea Food and Drug Administration (KFDA) for bioequivalence test indicating that Daewoong pregabalin capsule was bioequivalent to Lyrica$^{(R)}$ capsule.

• Journal of Pharmaceutical Investigation
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• 제39권1호
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• pp.65-71
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• 2009

The aim of the present study was to evaluate the bioequivalence of two domperidone maleate tablets, Motilium-$M^{(R)}$ Tablet (Janssen Korea Ltd., reference product) and $Toriem^{(R)}$ Tablet (Daewon Pharm. Co., Ltd., test product). Domperidone was extracted by liquid-liquid extraction using tert-butyl methyl ether and separated in less than 3 min on $C_{18}$ reverse-phase column using an isocratic elution. A tandem mass spectrometer, as detector, was used for quantitative analysis in positive mode by a multiple reaction monitoring mode to monitor the m/z $426.1{\rightarrow}119.1$ and the m/z $837.4{\rightarrow}158.2$ transitions for domperidone and the internal standard (roxithromycin), respectively. Calibration curves, from $0.05{\sim}50$ ng/mL of domperidone, showed correlation coefficients (r) higher than 0.9941. Intra day and inter day precision (C.V. %) for quality control were ranged from 10.04 to 16.09% and from 10.87 to 18.69%, respectively. The lower limit of quantification (LLOQ) of domperidone was 0.05 ng/mL. The method described is precise and sensitive and has been successfully applied to the study of bioequivalence of domperidone in 24 healthy Korean volunteers. Twenty-four healthy male Korean volunteers received a single dose of each medicine ($2{\times}12.72\;mg$ domperidone maleate) in a $2{\times}2$ crossover study. There was a one-week washout period between the doses. Plasma concentrations of domperidone were monitored for over a period of 24 hr after the administration. $AUC_{0-t}$ (the area under the plasma concentration-time curve) was calculated by the linear trapezoidal rule. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were compiled from the plasma concentration-time data. The 90% confidence intervals for the log transformed data were within acceptable range of log 0.8 to log 1.25 (e.g., $log\;0.92{\sim}log\;1.05$ for $AUC_{0-t}$, $log\;0.81{\sim}log\;1.05$ for $C_{max}$). The major parameters, $AUC_{0-t}$ and $C_{max}$ met the criteria of KFDA for bioequivalence indicating that $Toriem^{(R)}$ tablet is bioequivalent to Motilium-$M^{(R)}$ tablet.

• Journal of Pharmaceutical Investigation
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• 제36권5호
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• pp.343-348
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• 2006

The purpose of the present study was to evaluate the bioequivalence of two zolpidem tartrate tablets, Stilnox tablet(Sanofi-aventis Korea, reference product) and Zanilo tablet(ChoDang Pharm Co., Ltd., Korea, test product), according to the guidelines of Korea Food and Drug Administration(KFDA). After adding an internal standard(cimetropium), 250 ${\mu}L$ plasma samples were extracted using 1.3 mL of ethyl acetate. Extracted compounds were analyzed by HPLC with triple-quadrupole mass spectrometry. This method for determination of zolpidem is proved accurate and reproducible with the limit of quantitation of 1 ng/mL in human plasma. Twenty-four healthy male Korean volunteers received each medicine at the zolpidem tartrate dose of 10 mg in a $2{\times}2$ crossover study. There was one-week washout period between the doses. Plasma concentrations of zolpidem were monitored for over a period of 8 hr after the administration. $AUC_{0-t}$(the area under the plasma concentration-time curve) was calculated by the linear trapezoidal rule. $C_{max}$(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 $AUC_{0-t}$ and $C_{max}$. No significant sequence effect was found for all of the bio-availability parameters indicating that the crossover design was properly performed. The 90% confidence intervals for the log transformed data were acceptable range of log 0.8 to log 1.25(e.g., log 0.92-log 1.06 for $AUC_{0-t}$, log 0.96-log 1.13 for $C_{max}$). The major parameters, $AUC_{0-t}$ and $C_{max}$ met the criteria of KFDA for bioequivalence indicating that Zanilo tablet is bioequivalent to Stilnox tablet.

• 지구물리와물리탐사
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• 제8권1호
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• pp.112-117
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• 2005

물리검층은 석탄광 탐사에 일상적으로 적용된다. 현재 검층의 주요 적용 목적은 탄층의 심도 탐지와 탄질, 층서 및 암반강도의 정성적 추정이다. 그러나 만약 정량적 해석이 이루어진다면 더 많은 정보가 얻어질 수 있는데, 정량적 해석의 이해를 돕기 위해, 검층 반응을 Sydney Basin과 Bowen Basin의 호주산 검은 석탄(black coal) 광산지역에서 흔히 발견되는 쇄설퇴적암의 광물조성에 따라 논의하였으며, 검층 반응은 충분한 신뢰도로 광물조성에 대비될 수 있음을 알았다. 해석의 모호성은 만약 모든 종류의 검층자료가 있다면 더 잘 해결될 수 있을 것이다. 음파검층에서 측정된 속도와 계산값을 비교함으로써 일관성을 검토하는 방법 또한 서술하였다. 정량해석의 중요한 목적은 지질공학적 특성화이며, 이 논문에서는 물리검층으로부터 유추될 수 있는 물리적 성질을 고려한 쇄설암의 분류 시스템을 제안하였다.

• Journal of Radiation Protection and Research
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• 제46권1호
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• pp.8-13
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• 2021

Background: Salmonella enteritidis (SE) was the main cause of the pandemic of foodborne salmonellosis. The surface of eggs' shells can be contaminated with this bacterium; however, washing them with sodium hypochlorite solution not only reduces their flavor but also heavily impacts the environment. An alternative to this is surface sterilization using low-energy electron beam. It is known that irradiation with 1 kGy resulted in a significant 3.9 log reduction (reduction factor of 10,000) in detectable SE on the shell. FAO/IAEA/WHO indicates irradiation of any food commodity up to an overall average dose of 10 kGy presents no toxicological hazard. On the other hand, the Food and Drug Administration has deemed a dose of up to 3 kGy is allowable for eggs. However, the maximum dose permitted to be absorbed by an edible part (i.e., internal dose) is 0.1 Gy in Japan and 0.5 Gy in European Union. Materials and Methods: The electron beam (EB) depth dose distribution in the eggshell was calculated by the Monte Carlo method. The internal dose was also estimated by Monte Carlo simulation and experimentation. Results and Discussion: The EB depth dose distribution for the eggshells indicated that acceleration voltages between 80 and 200 kV were optimal for eggshell sterilization. It was also found that acceleration voltages between 80 and 150 kV were suitable for reducing the internal dose to ≤ 0.10 Gy. Conclusion: The optimum irradiative conditions for sterilizing only eggshells with an EB were between 80 and 150 kV.

• 한국식품위생안전성학회지
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• 제35권5호
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• pp.459-467
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• 2020

본 연구에서는 신선편의식품을 구매한 뒤 집으로 귀가해서 냉장고에 보관하거나 섭취하는데 소요되는 시간과 그에 따른 신선편의식품 내.외부의 온도변화와 미생물학적 변화를 관찰하였다. 시판 중인 신선편의 식품에 대해 위생지표세균인 일반세균, 대장균군 및 대장균, 병원성 미생물인 B. cereus, S. aureus, Salmonella spp., L. monocytogenes를 분석하였다. 설문조사 결과 신선편의식품을 구매 후 귀가 또는 섭취에 소요되는 시간이 최대 3시간 소요되는 것으로 확인되어, 차량 트렁크 내에서 최대 3시간 동안 보관한 결과 차량 트렁크 내부 최고 온도가 봄(3월) 19℃, 여름(7월) 44℃, 가을(9월) 31.3℃, 겨울(2월) 17.6℃로 각각 확인되었으며, 차량 트렁크에서 보관한 신선편의식품의 품온은 최대 봄 18.5℃, 여름 42℃, 가을 29.2℃, 겨울 16.8℃로 확인되었다. 차량 트렁크에 최대 3시간 보관한 신선편의식품의 일반세균수는 봄 3.41 log CFU/g, 여름 4.32 log CFU/g, 가을과 겨울은 각각 3.81 log CFU/g, 3.36 log CFU/g으로 확인되었다. 그 외의 대장균군 및 대장균, B. cereus, Salmonella spp., L. monocytogenes균은 검출되지 않았지만 S. aureus는 여름과 가을철에는 신선편의식품을 1시간만 차량에 보관하더라도 검출되었고, 봄과 겨울은 2시간 이상 차량 트렁크에 보관하였을 때 검출되었다. 이동용기로 흔히 사용되는 종이박스와 스티로폼 박스 내부가 알루미늄필름으로 코팅된 종이 박스를 이용하여 얼음 첨가여부에 따른 이동용기 온도변화 실험과 이동 중 S. aureus의 증식여부를 확인한 결과 스티로폼 박스에서 내부 온도변화가 가장 낮게 유지되었고, 시간 경과에 따른 미생물의 증식도 가장 적게 나타남을 확인할 수 있었다. 이상의 결과로 볼 때 신선편의식품 소비자들에게 구매 후 안전한 섭취를 위해 보관 온도나 시간에 대한 가이드라인과 이동용기를 이용한 신선편의식품의 온도관리에 대한 정보를 제공하여 식품의 안전성을 높이는 홍보가 필요할 것으로 판단된다.

• Korean Journal of Radiology
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• 제22권12호
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• pp.1974-1984
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• 2021

Objective: This study aimed to compare the efficacy between no-touch (NT) radiofrequency ablation (RFA) and conventional RFA using twin internally cooled wet (TICW) electrodes in the bipolar mode for the treatment of small hepatocellular carcinomas (HCC). Materials and Methods: In this single-center, two-arm, parallel-group, prospective randomized controlled study, we performed a 1:1 random allocation of eligible patients with HCCs to receive NT-RFA or conventional RFA between October 2016 and September 2018. The primary endpoint was the cumulative local tumor progression (LTP) rate after RFA. Secondary endpoints included technical conversion rates of NT-RFA, intrahepatic distance recurrence, extrahepatic metastasis, technical parameters, technical efficacy, and rates of complications. Cumulative LTP rates were analyzed using Kaplan-Meier analysis and the Cox proportional hazard regression model. Considering conversion cases from NT-RFA to conventional RFA, intention-to-treat and as-treated analyses were performed. Results: Enrolled patients were randomly assigned to the NT-RFA group (37 patients with 38 HCCs) or the conventional RFA group (36 patients with 38 HCCs). Among the NT-RFA group patients, conversion to conventional RFA occurred in four patients (10.8%, 4/37). According to intention-to-treat analysis, both 1- and 3-year cumulative LTP rates were 5.6%, in the NT-RFA group, and they were 11.8% and 21.3%, respectively, in the conventional RFA group (p = 0.073, log-rank). In the as-treated analysis, LTP rates at 1 year and 3 years were 0% and 0%, respectively, in the NT-RFA group sand 15.6% and 24.5%, respectively, in the conventional RFA group (p = 0.004, log-rank). In as-treated analysis using multivariable Cox regression analysis, RFA type was the only significant predictive factor for LTP (hazard ratio = 0.061 with conventional RFA as the reference, 95% confidence interval = 0.000-0.497; p = 0.004). There were no significant differences in the procedure characteristics between the two groups. No procedure-related deaths or major complications were observed. Conclusion: NT-RFA using TICW electrodes in bipolar mode demonstrated significantly lower cumulative LTP rates than conventional RFA for small HCCs, which warrants a larger study for further confirmation.

• 대한한방내과학회지
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• 제29권3호
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• pp.778-786
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• 2008

Objectives : This study was to investigate the short time effect of caffeine on heart rate variability(HRV) and the effect of Neiguan(PC6) acupuncture stimulation on HRV. Methods : 27 healthy adult volunteers were randomly allocated to two groups: Neiguan group (N=13) or placebo group (N=14). The study was carried out under a randomized double-blinded placebo-controlled trial method. Each group orally received the same tablets with 200 mg caffeine. After 1 hour, acupuncture was applied to the Neiguan(PC6) points for the Neiguan group, and for the placebo group was applied to a non-acupuncture point. Both groups were estimated with HRV 3 times, before and after caffeine ingestion, 20 minutes after acupuncture stimulation. Results : After taking caffeine, pulse rate, mean-HRV, and pNN50(the proportion derived by dividing NN50 by the total number of NN intervals) decreased, SDNN(standard deviation of all normal-to-normal (NN) intervals), RMSSD (the root square of successive differences), TP log, HF(high frequency), and HRV index was increased. There were significant changes to the autonomic nervous system after taking caffeine. There were no significant differences between the two groups after acupuncture at Neiguan. Conclusion : Caffeine could induce general activation of the autonomic nervous system. Neiguan acupuncture stimulation may not have significant influence on the autonomic nervous system.

• 대한전기학회:학술대회논문집
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• 대한전기학회 2002년도 합동 추계학술대회 논문집 정보 및 제어부문
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• pp.39-41
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• 2002

Management of internal Internet servers is increasingly becoming an important task. According to meet this requirement, they use service log analysis tools and network monitoring tools. But these are not enough to produce advanced management information considering contents of Internet services. Therefor we propose a system and let it detect Internet server systems existing in internal network and individuate those systems with providing profile. Internet server profile includes system's basic information, network traffic information, and Internet service usage information.

• Journal of Pharmaceutical Investigation
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• 제37권5호
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• pp.315-321
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• 2007

The purpose of the present study was to evaluate the bioequivalence of two lercanidipine hydrochloride tablets, Zanidip tablet (LG Life Sciences Ltd., Korea, reference drug) and Samchundang Lercanidipine tablet 10 mg (Sam Chun Dang Pharm. Co. Ltd., Korea, test drug), according to the guidelines of Korea Food and Drug Administration (KFDA). After adding an internal standard (amlodipine maleate) to human serum, serum samples were extracted using hexan-isoamyl alcohol (100:1, v/v). Compounds were analyzed by liquid chromatography/tandem mass spectrometry. This method showed linear response over the concentration range of 0.05-20 ng/mL with correlation coefficient of 0.9999. The lower limit of quantitation using 0.5 mL of serum was 0.05 ng/mL which was sensitive enough for pharmacokinetic studies. Thirty healthy male Korean volunteers received each medicine at the lercanidipine hydrochloride dose of 20 mg in a $2\;{\times}\;2$ crossover study. There was a one-week washout period between the doses. Serum concentrations of lercanidipine were monitored by an LC/MS/MS fer over a period of 24 hr after the administration. $AUC_t$ (the area under the serum concentration-time curve from time 0 to 24 hr) was calculated by the linear trapezoidal rule method. $C_{max}$ (the maximum serum drug concentration) and $T_{max}$ (the time to reach $C_{max}$) were compiled from the serum 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 Samchundang Lercanidipine/Zanidip were log 0.9505-log 1.2258 and log 0.9987-log 1.2013, respectively. These values were within the acceptable bioequivalence intervals of log 0.80-log 1.25. Thus, the criteria of the KFDA guidelines for the bioequivalence was satisfied, indicating Samchundang Lercanidipine tablet 10 mg and Zanidip tablet are bioequivalent.