• Journal of Microbiology and Biotechnology
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• 제15권6호
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• pp.1323-1329
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• 2005

A mathematical model was developed for predicting the growth kinetics of Listeria monocytogenes in tryptic soy broth (TSB) as a function of combined effects of temperature, pH, and NaCl. The TSB containing four different concentrations of NaCl (2, 4, 5, and $10\%$) was initially adjusted to six different pH levels (pH 5, 6, 7, 8, 9, and 10) and incubated at 4, 10, 25, or 37$^{circ}C$. In all experimental variables, the primary growth curves were well fitted ($r^{2}$=0.982 to 0.998) to a Gompertz equation to obtain the lag time (LT) and specific growth rate (SGR). Surface response models were identified as appropriate secondary models for LT and SGR on the basis of coefficient determination ($r^{2}$=0.907 for LT, 0.964 for SGR), mean square error (MSE=3.389 for LT, 0.018 for SGR), bias factor ($B_{1}$B,=0.706 for LT, 0.836 for SGR), and accuracy factor ($A_{f}$=1.567 for LT, 1.213 for SGR). Therefore, the developed secondary model proved reliable predictions of the combined effect of temperature, NaCl, and pH on both LT and SGR for L. monocytogenes in TSB.

• Journal of Pharmaceutical Investigation
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• 제39권1호
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• pp.73-78
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• 2009

A simple LC-MS/MS method of rabeprazole in human plasma was developed and validated. Rabeprazole and Internal standard (I.S), omeprazole, were extracted from human plasma by liquid liquid extraction, chromatographic separation of rabaprazole in plasma was achieved at $45^{\circ}C$ with a Shiseido UG120 $C_{18}$ column and methanol-10 mM ammonium acetate buffer (pH 9.42 with ammonium water), as mobile phase. Rabeprazole produced a protonated precursor ion [$(M+H)^+$] at m/z 360.10 and corresponding product ion at m/z 242.21. Internal standard produced a protonated precursor ion [$(M+H)^+$] at 346.09 and corresponding product ion at m/z 198.09. This method showed linear response over the concentration range of $1{\sim}500\;ng/mL$ with correalation coefficient greater than 0.99. The lower limit of quantitation (LLOQ) using 0.2 mL plasma was 1 ng/mL, which was sensitive enough for pharmacokinetics studies. The method was specific and validated with a limit of quantitation of 1 ng/mL. The intra-day and inter-day precision and accuracy were acceptable for all samples including the LLOQ. The applicability of the method was demonstrated by analysis of plasma after administration of a single 10 mg dose to 36 healthy subject. From the plasma rabeprazole concentration versus time curves, the mean $AUC_t$ (The area under the plasma concentration-time curve from time 0 to 12 hr ) was $691.36{\pm}321.88\;ng{\cdot}hr/mL$, $C_{max}$ (maximum plasma drug concentration) of $353.21{\pm}131.52\;ng/mL$ reached $3.4{\pm}1.1\;hr$ after adiministration. The mean biological half-life of rabeprazole was $1.37{\pm}0.75\;hr$. Based on the results, this simple method could readily be used in pharmacokinetics studies.

• Journal of Pharmaceutical Investigation
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• 제36권6호
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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.

• 분석과학
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• 제24권2호
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• pp.142-149
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• 2011

Resveratrol을 GC/TOF-MS를 이용하여 대사체를 확인한 결과, 두 개의 phenyl기를 연결하는 이중결합이 단일결합으로 환원된 구조로 추정되었다. 또한, GC/MSD를 이용하여 resveratrol 및 내인성스테로이드의 분석법에 대한 유효성을 점검한 결과, 회수율은 96.47 - 114.74%의 범위로 나타났으며, intra-day와 inter-day의 정밀도는 1.40 - 10.87%과 1.10 - 10.93% 그리고 정확도는 80.03 - 119.92%과 80.02 - 119.56%로 조사되었고, 모두 0.996이상의 직선성을 나타내어 유효한 분석 방법으로 검증되었다. 한편, 지원자들에게 resveratrol을 경구투여 한 요시료로부터 resveratrol과 그 대사체에 대한 상관성을 조사해본 결과, 요중 최대농도 도달시간이 일반적인 약물(1 - 2시간) 보다 긴 10 - 15시간에 나타났으며, 대사체로의 전환율은 남성보다 여성이 높게 나타났다. 한편, 내인성 스테로이드는 약물 복용 후 20시간 까지는 resveratrol 및 그 대사체와 다소 유사한 분비형태를 나타내었으며, estrone과 estradiol의 경우 여성이 남성에 비해 이 약물에 대한 민감성이 높게 나타났다. 그 외의 내인성 스테로이드는 유의할만한 차별된 분비형태의 변화가 나타나지 않았다. 따라서 resveratrol의 경우 약물의 활성이 남성보다는 여성에게 유의한 영향을 미치는 것으로 추측되었다.

• 대한화장품학회지
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• 제42권1호
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• pp.65-73
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• 2016

대한민국 식품의약품안전처(식약처)는 포름알데하이드 분석법으로 2,4-dinitrophenylhydrazine(DNPH) 유도체화-고성능액체크로마토그래프법(HPLC)을 고시하고 있다. 본 연구는 고시법의 복잡한 시료 전처리 과정을 개선하여 화장품 분석에 편리하게 사용할 수 있는 유도체화법을 개발하고자 수행되었다. 전처리법을 간단하게 하기 위하여 pH, 시간 및 온도 등 반응조건을 최적화하였다. 이 전처리법은 초산염 완충액(pH 5.0)을 사용한 검액의 pH 조정, 디클로로메탄을 사용한 액-액 분획 그리고 감압농축기를 사용한 증발건조와 같이 식약처 고시법의 복잡한 과정이 필요 없다. 유도체화 과정을 통하여 생성된 formaldehyde dinitrophenylhydrazone(formaldehyde-DNP)는 식약처의 시험방법을 약간 변형한 역상 HPLC법으로 분리하고 정량하였다. 2 ~ 40 ppm 농도 범위의 표준액들을 가지고 수행한 검량선 작성 결과, 본 시험법은 상관계수 값이 0.9999로 좋은 직선성을 보여주었다. 본 실험의 최소검출한계(LOD)와 최소정량한계(LOQ)는 각각 0.2 ppm과 0.5 ppm이었다. 또한 회수율 실험결과는 실험방법이 매우 정확하고 재현성이 높음을 보여주었다. 따라서 본 연구에서 제안된 시험법은 화장품 중 포름알데하이드를 신속하게 분석하는데 적용될 수 있을 것이다.

• 한국의학물리학회지:의학물리
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• 제16권2호
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• pp.53-61
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• 2005

본 연구에서는 kV X-선에 대하여 원통형전리함의 선질인자를 몬테칼로 계산과 측정으로 결정하였다. 대상 X-선은 KFDA에 설치되어 있으며 에너지스펙트럼과 선질이 명시된 $60\~300kV$ 범위의 X-선(ISO-4037)이었으며, 전리함은 PTW N23333과 N30001이었다. 이론적 계산과 몬테칼로 계산으로 구한 공기커마와 공동의 흡수선량으로부터 IAEA프로토콜의 $R_{\mu}$와 $R_{Q,Q_{0}}$인자를 결정하였다. 두 전리함의 반응 범위는 $80\~250kV$ 영역에서 모두 $\pm3\~4\%$를 보였으나, N30001 전리함의 경우에 $110\~300kV$ 영역에서 $\pm1.7\%$로서 평탄한 특성을 보였다. 본 연구로부터 kV X-선에 대한 선량평가에 대하여 고찰할 수 있었으며, 프로토콜의 적용을 위하여 에너지의존성의 평가가 중요함을 알 수 있었다.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제43권4호
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• pp.229-238
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• 2017

Objectives: The primary purpose of this study was to investigate the factors related with additional administration of sedative agent during intravenous conscious sedation (IVS) using midazolam (MDZ). The secondary purpose was to analyze the factors affecting patient satisfaction. Materials and Methods: Clinical data for 124 patients who had undergone surgical extraction of mandibular third molar under IVS using MDZ were retrospectively investigated in this case-control study. The initial dose of MDZ was determined by body mass index (BMI) and weight. In the case of insufficient sedation at the beginning of surgery, additional doses were injected. During surgery, peripheral oxygen saturation, bispectral index score (BIS), heart rate, and blood pressure were monitored and recorded. The predictor variables were sex, age, BMI, sleeping time ratio, dental anxiety, Pederson scale, and initial dose of MDZ. The outcome variables were additional administration of MDZ, observer's assessment of alertness/sedation, intraoperative amnesia, and patient satisfaction. Descriptive statistics were computed, and the P-value was set at 0.05. Results: Most patients had an adequate level of sedation with only the initial dose of MDZ and were satisfied with the treatment under sedation; however, 19 patients needed additional administration, and 13 patients were unsatisfied. In multivariable logistic analysis, lower age (odds ratio [OR], 0.825; P=0.005) and higher dental anxiety (OR, 5.744; P=0.003) were related to additional administration; lower intraoperative amnesia (OR, 0.228; P=0.002) and higher BIS right before MDZ administration (OR, 1.379; P=0.029) had relevance to patient dissatisfaction. Conclusion: The preoperative consideration of age and dental anxiety is necessary for appropriate dose determination of MDZ in the minor oral surgery under IVS. The amnesia about the procedure affects patient satisfaction positively.

• Biomolecules & Therapeutics
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• 제6권3호
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• pp.289-295
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• 1998

The bioequivalence of two nilvadipine products was evaluated in 16 normal male volunteers (age 22-32 yr, body weight 57-80 kg) following sidle oral dose. Test product was Overca $l_{R}$ tablet (Choong-Wae Pharm. Corp., Korea) and reference product was Nivadi $l_{R}$ tablet (Hyundai Pharm. Corp., Korea). Both products contain 4 mg of nilvadipine. One tablet of the test or the reference product was administered to the volunteers, respectively, by randomized two period cross-over study (2$\times$2 Latin square method). The determination of nilvadipine was accomplished using a validated capillary column GC with electron-capture detection. As a result of the assay validation, the quantiflcation of nilvadipine in human plasma by this technique was possible down to 0.5 ng/ml using 1 ml of plasma. Absolute overall recovery from five replicate analyses of nilvadipine-spiked sample were 88.4$\pm$ 10.24% (mean$\pm$ 5.D.) for human plasma of 10 ng/ml. The coefficients of variation (C.V.) were less than 20% and the actual concentration of nilvadipine measured by GC ranged from 80 to 99% in all plasma. Average drug concentrations at each sampling time and pharmacokinetic parameters calculated were not significantly different between two products (p>0.05); the area under the curve from time zero to 8 hr (AUCo-$_{8 hr}$) (22.8$\pm$5.90 vs 22.2$\pm$6.10 ng . hr/ml), maximum plasma concentration ( $C_{max}$) (10.0$\pm$2.85 vs 9.3$\pm$3.28 ng/ml) and time to reach maximum plasma concentration ( $T_{max}$) (1.2$\pm$0.31 vs 1.3 $\pm$0.47 hr). The differences of mean AU $Co_{8hr}$ $C_{max}$, and $T_{max}$ between the two products (2.25, 7.65, and 10.30%, respectively) were less than 20%. The power (1-$\beta$) and treaeent difference (7) for AU $Co_{8hr}$, and $C_{max}$ were more than 0.8 and less than 0.2, respectively. Although the power for Tmax was under 0.8, Tm\ulcorner of the two products was not significantly different from each other (p>0. 05). These results suggest that the bioavailability of Overeat tablet is not significantly different from that of Nivadil tablet. Therefore, two products are bioequivalent based on the current results.sults.lts.lts.lts.

• 한국식품과학회지
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• 제41권3호
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• pp.258-264
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• 2009

본 연구에서는 밀 시료에서 면역친화컬럼을 이용한 HPLC분석법으로 데옥시니발레놀을 분석함에 있어서 발생될 수 있는 측정 불확도를 GUM 지침에 따라 산정하였다. 분석과정에서의 불확도 요인은 시료량 측정, 최종 시료부피, 보관표준용액, 작업표준용액, 표준용액, 기기, 매질, 검량선 작성으로 구분하였다. 불확도 요인의 구성요인은 저울의 안정성, 분해능, 재현성, 표준물질의 순도, 분자량, 농도, 표준용액 희석, 검량선, 회수율 및 분석기기의 재현성 등이 작용하였다. 공시료에 데옥시니발레놀 300 ${\mu}g/kg$을 첨가하여 분석한 결과 $255.29{\pm}71.62$ ${\mu}g/kg$으로 측정되었다. 확장불확도는 합성표준불확도 35.81 ${\mu}g/kg$에 포함인자(k=2, 신뢰수준 95%)를 곱하여 산출하였다. 밀에서 데옥시니발레놀을 분석함에 있어 불확도에 영향을 주는 주요인자는 시료의 회수율과 검량선 작성인 것으로 파악되었다. 따라서 밀 시료에서 데옥시니발레놀 분석의 정밀성을 높이기 위해서는 회수율과 검량선 작성에 영향을 끼칠 수 있는 면역친화컬럼에 의한 시료의 정제과정과 표준물질의 희석과정에 주의를 기울이고 주기적으로 마이크로피펫을 교정하는 등 세심한 관리가 필요할 것으로 판단된다.

• Toxicological Research
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• 제29권1호
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• pp.53-60
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• 2013

Studies on milk transfer of drugs in non-human primates (NHPs) are among the crucial components in the assessment of peri- and postnatal toxicity because of the similarity between NHPs and humans. To evaluate the milk transfer of valproic acid (VPA) in NHPs, the toxicokinetics of VPA, an antiepileptic drug, were studied in pregnant cynomolgus monkeys. VPA was administered once daily to pregnant cynomolgus monkeys at doses of 0, 30, 90, and 270 mg/kg by oral gavage from Day 100 of gestation (GD 100) to Day 31 of lactation (LD 31). Concentrations of VPA and its metabolite, 4-ene-VPA, in the maternal plasma on GD 100, GD 140, and LD 30, and concentrations of VPA and 4-ene-VPA in the offspring plasma and milk on LDs 30 and 31, respectively, were quantified using liquid chromatography tandem mass spectrometry (LC/MS/MS). After administration of a single oral dose of VPA to pregnant monkeys on GD 100, the concentrations of VPA and 4-ene-VPA were generally quantifiable in the plasma of all treatment groups up to 24 hr after administration, which showed that VPA was absorbed and that the monkeys were systemically exposed to VPA and 4-ene-VPA. After administration of multiple doses of VPA to the monkeys, VPA was detected in the pup's plasma and in milk taken on LD 30 and LD 31, respectively, which showed that VPA was transferred via milk, and the pup was exposed to VPA. Further, the concentration of VPA in the milk increased with an increase in the dose. Extremely low concentrations of 4-ene VPA were detected in the milk and in the pup plasma. In conclusion, pregnant monkeys were exposed to VPA and 4-ene-VPA after oral administration of VPA at doses of 30, 90, and 270 mg/kg/day from GD 100 to LD 31. VPA was transferred via milk, and the VPA exposure to the pup increased with an increase in the dose of VPA. The metabolite, 4-ene VPA, was present in extremely low concentrations (< 0.5 ${\mu}g/ml$) in the milk and in the pup plasma. In this study, we established methods to confirm milk transfer in NHPs, such as mating and diagnosis of pregnancy by examining gestational sac with ultrasonography, collection of milk and pup plasma and determination of toxicokinetics, using cynomolgus monkeys.