• 생물정신의학
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• 제18권2호
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• pp.95-100
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• 2011

Objectives To evaluate the drug interactions between aripiprazole and haloperidol, authors investigated plasma concentrations of those drugs by genotypes. Method Fifty six patients with a confirmed Diagnostic and Statistical Manual of Mental Disorders 4th edition diagnosis of schizophrenia were enrolled in this eight-week, double blind, placebo-controlled study. Twenty-eight patients received adjunctive aripiprazole treatment and twenty-eight patients received placebo while being maintained on haloperidol treatment. Aripiprazole was dosed at 15 mg/day for the first 4 weeks, and then 30 mg for the next 4 weeks. The haloperidol dose remained fixed throughout the study. Plasma concentrations of haloperidol and aripiprazole were measured by high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) at baseline, week 1, 2, 4 and 8. $^*1$, $^*5$, and $^*10$ B alleles of CYP2D6 and $^*1$ and $^*3$ alleles of CYP3A5 were determined. The Student's T-test, Pearson's Chi-square test, Wilcoxon Rank Sum test and Logistic Regression analysis were used for data analysis. All tests were two-tailed and significance was defined as an alpha < 0.05. Results In the frequency of CYP2D6 genotype, $^*1/^*10$ B type was most frequent (36.5%) and $^*1/^*1$ (30.8%), $^*10B/^*10B$ (17.3%) types followed. In the frequency of CYP3A5 genotype, $^*3/^*3$ type was found in 63.5% of subjects, and $^*1/^*3$ type and $^*1/^*1$ were 30.8% and 5.8% respectively. The plasma levels of haloperidol and its metabolites did not demonstrate significant time effects and time-group interactions after adjunctive treatment of aripiprazole. The genotypes of CYP2D6 and 3A5 did not affect the plasma concentration of haloperidol in this trial. No serious adverse event was found after adding aripiprazole to haloperidol. Conclusion No significant drug interaction was found between haloperidol and aripiprazole. Genotypes of CYP2D6 and 3A5 did not affect the concentration of haloperidol after adding aripiprazole.

• 한국식품영양과학회지
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• 제45권6호
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• pp.828-834
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• 2016

경남 합천 일대에서 재배된 보리수나무(Elaeagnus umbellata Thunb.)의 생리활성을 부위별(열매, 잎, 줄기)로 평가한 결과는 다음과 같다. 항산화 특성을 측정한 결과, 총폴리페놀 함량이 높게 나타난 줄기(829.6 mg/g) 에탄올 추출물에서 DPPH 라디칼 소거능($EC_{50}=54.04{\mu}g/mL$)이 가장 우수하였다. 유리 아미노산 분석에서는 잎(6,179.12 mg/100 g) 에탄올 추출물이 열매(378.88 mg/100 g)와 줄기(1,211.69 mg/100 g) 에탄올 추출물보다 유리 아미노산 함량이 높았으며, 열매의 proline, 잎의 asparagine 및 줄기의 GABA가 대표적인 유리 아미노산인 것을 확인하였다. LC-MS/MS를 이용한 주요 페놀 성분 분석에서는 잎 에탄올 추출물에서 gallic acid, 줄기 에탄올 추출물에서 catechin의 함량이 가장 높았으며, HepG2 cell과 Chang cell의 암세포 증식억제 효과를 측정한 결과 잎 에탄올 추출물이 HepG2에 특이적으로 높은 억제 활성이 나타났다. 향후 보리수나무를 국내 우수 자원으로 활용하기 위해서는 추가로 다양한 암세포에 대한 활성 차이, 부위별 활성 물질의 구명 및 작용 기전 등에 대한 계속된 연구가 수행되어야 할 것이다.

• 분석과학
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• 제25권1호
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• pp.19-24
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• 2012

LC-MS/MS를 이용하여 혈장과 소변 중 에르타페넴의 신속하고 정확한 분석법을 개발하고 이 분석법에 대한 검증을 수행하였다. 혈장과 소변 분석을 위하여 내부 표준 물질인 세프타지딤을 첨가한 후 메탄올로 단백질을 침전시키고, 그 상층액을 취하여 메탄올로 희석하여 LC-MS/MS로 분석하였다. MS/MS의 MRM (multiple reaction monitoring) 방법을 이용하여 혈장과 소변 중의 에르타페넴을 어떠한 분석의 방해물 없이 선택적으로 검출할 수 있었다. 혈장 중 에르타페넴의 표준 검량선은 1~100 ${\mu}g/mL$의 농도 범위에서 우수한 직선성($r^2$ = 0.9996)을 보였으며, 일내, 일간 재현성은 변동계수 8.9% 이하, 정확성은 97.2~106.2% 이었다. 또한 소변 중 에르타페넴의 분석 결과는 좋은 상관관계($r^2$ = 0.9992)를 보였고, 일내, 일간 재현성이 변동계수 7.2% 이하, 정확성이 97.9~111.6% 이었다. 결과적으로 에르타페넴의 약동학 연구에 적용되기에 충분한 감도와 특이성, 직선성, 정밀성 및 정확성을 가지고 있음을 확인하였다.

• 한국식품과학회지
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• 제48권6호
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• pp.531-535
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• 2016

천속단과 한속단은 명칭이 유사하여 '속단'으로 통칭하여 판매되고 있으나, 종과 속이 서로 다른 약재일 뿐만 아니라 함유 성분이 다르므로 주의가 필요하다. 천속단은 골격강화, 골절치료 작용이 있는 한약재로 식품원료로는 사용할 수 없으나, 한속단의 뿌리와 잎은 식품원료로 사용이 가능하다. 본 연구에서는 식품 중 천속단 혼입여부 판별을 위하여 LC-MS/MS를 이용한 동시분석법을 개발하였으며, 선택성, 직선성, 검출한계, 정량한계, 정확성, 정밀성을 검토하였다. 국내 유통중인 식품 중 어린이 키성장을 표방하는 제품 17건을 구매하여 천속단 혼입여부에 대한 실태조사를 하였다. 분석결과 17건의 시료 중 5건의 시료에서 천속단이 검출되었으며, 천속단 지표성분의 함량은 loganin $0.19-14.45{\mu}g/mL$, sweroside $0.13-4.61{\mu}g/mL$, akebia saponin D $0.59-19.29{\mu}g/mL$이었다. 본 연구에서 개발된 동시분석법은 식품 중 불법 혼입된 천속단을 간단하면서도 신속하게 판별하는데 도움이 될 것으로 사료된다.

• 한국환경농학회지
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• 제39권3호
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• pp.246-252
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• 2020

BACKGROUND: Pesticides are broadly used to control weeds and pests, and the residues remaining in crops are managed in accordance with the MRLs (maximum residue limits). Therefore, an analytical method is required to quantify the residues, and we conducted a series of analyses to select and validate the quick and simple analytical method for tolpyralate in five agricultural products using QuEChERS (quick, easy, cheap, effective, rugged and safe) method and LC-MS/MS (liquid chromatography-tandem mass spectrometry). METHODS AND RESULTS: The agricultural samples were extracted with acetonitrile followed by addition of anhydrous magnesium sulfate, sodium chloride, disodium hydrogencitrate sesquihydrate and trisodium citrate dihydrate. After shaking and centrifugation, purification was performed with d-SPE (dispersive-solid phase extraction) sorbents. To validate the optimized method, its selectivity, linearity, LOD (limit of detection), LOQ (limit of quantitation), accuracy, repeatability, and reproducibility from the inter-laboratory analyses were considered. LOQ of the analytical method was 0.01 mg/kg at five agricultural products and the linearity of matrix-matched calibration were good at seven concentration levels, from 0.0025 to 0.25 mg/L (R²≥0.9980). Mean recoveries at three spiking levels (n=5) were in the range of 85.2~112.4% with associated relative standard deviation values less than 6.2%, and the coefficient of variation between the two laboratories was also below 13%. All optimized results were validated according to the criteria ranges requested in the Codex Alimentarius Commission (CAC) and Ministry of Food and Drug Safety (MFDS) guidelines. CONCLUSION: In conclusion, we suggest that the selected and validated method could serve as a basic data for detecting tolpyralate residue in imported and domestic agricultural products.

• 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.

• Journal of Pharmaceutical Investigation
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• 제40권2호
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• pp.125-131
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• 2010

A bioequivalence study of LANIDIEM$^{(R)}$ tablet 4 mg (Samil. Co., Ltd.) to Vaxar$^{(R)}$ tablet 4 mg (GlaxoSmithKline Co., Ltd.) was conducted according to the guidelines of Korea Food and Drug Administration (KFDA). Forty healthy male Korean volunteers were enrolled in the study and thirty six volunteers completed the study according to the protocol. Thirty six volunteers received each medicine at the lacidipine dose of 4 mg in a $2{\times}2$ crossover study. There was one week wash-out period between the doses. Plasma concentrations of lacidipine were monitored by a high performance liquid chromatography - tandem mass spectrometry (LC-MS/MS) for over a period of 24 hours after drug administration. $AUC_t$ (the area under the plasma concentration-time curve from time zero to 24 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 LANIDIEM$^{(R)}$/Vaxar$^{(R)}$ were log 0.8102~log 1.0417 and log 0.8493~log 1.1439, respectively. These values were within the acceptable bioequivalence intervals of log 0.80~log 1.25. Thus, our study demonstrated the bioequivalence of LANIDIEM$^{(R)}$ tablet 4 mg and Vaxar$^{(R)}$ tablet 4 mg with respect to the rate and extent of absorption.

• 한국식품위생안전성학회지
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• 제32권5호
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• pp.389-395
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• 2017

루이보스티에서 5종의 phenolic acid (gallic acid, chlorogenic acid, caffeic acid, p-coumaric acid, trans-ferulic acid)와 9종의 flavonoid (procyanidin b1, aspalathin, rutin, vitexin, hyperoside, isoquercitrin, luteolin, quercetin, chrysoeriol)를 UPLC-MSMS를 이용하여 동시 분석하였다. 14종 페놀릭류를 동시 분석하기 위하여 기기조건과 유효성을 검증하였고 확립된 분석방법을 이용하여 시중에 유통중인 루이보스티 30건을 채취하여 페놀릭류를 분석하였다. 루이보스티 1 g 혹은 1티백에 뜨거운 물 100 mL을 가하여 3분, 6분, 30분이 경과 후 그리고 차가운 물 ($25-30^{\circ}C$)에 30분 우려낸 루이보스티의 페놀릭류 함량을 구하였다. 루이보스티에서 전체 실험대상 페놀릭류 중 rutin과 aspalathin이 가장 많이 추출되어 나왔으며 각각 물질의 함량은 제품별로 달랐다. 페놀릭류 성분의 추출효율은 14종 페놀릭류의 총합 기준으로 뜨거운 물 30분 > 6분 > 3분 > 차가운 물 30분 순으로 높았다.

• 한국식품위생안전성학회지
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• 제35권5호
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• pp.447-451
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• 2020

본 연구에서는 2018년 충남지역에서 생산, 출하되는 수산물에 대해 잔류동물용의약품 실태를 조사하였다. 수산물 115건을 대상으로 식품공전 수산물 중 동물용의약품 동시 다성분 시험법으로 분석이 가능한 29종의 잔류동물용의약품을 분석하였다. 115건의 수산물 중 9건에서 6종의 잔류동물용의약품이 검출되었으며, 검출률은 7.8%이었다. 검출된 잔류동물용의약품은 옥소린산, 엔로플록사신이 가장 많이 검출되었으며 시프로플록사신, 설파디아진, 플루메퀸, 옥시테트라사이클린이 각각 검출되었다. 미꾸라지 검체 1건에서 엔로플록사신이 잔류기준을 초과하였으나 전체적으로 안전한 수준으로 평가되었다. 그렇지만 잔류동물용의약품 검출률이 높아지는 추세이고 종류 또한 다양해지고 있어 지속적인 모니터링이 필요하다.

• 대한유전성대사질환학회지
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• 제15권1호
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• pp.40-43
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• 2015

Short-chain acyl-CoA dehydrogenase (SCAD) deficiency is an autosomal recessive mitochondrial disorder of fatty acid oxidation associated with mutations in the ACADS gene. While patients diagnosed clinically have a variable clinical presentation, patients diagnosed by newborn screening are largely asymptomatic. We describe here the case of a 1-year-old male patient who was detected by newborn screening and diagnosed as SCAD deficiency. Spectrometric screening for inborn errors of metabolism at 72hrs after birth showed elevated butyrylcarnitine (C4) level of 1.69 mol/L (normal, <0.83 mol/L), C4/C2 ration of 0.26 (normal, <0.09), C5DC+C60H level of 39 mol/L (normal, <0.28 mol/L), and C5DC/C8 ration of 7.36 (normal, <4.45). The follow-up testing at 18 days of age were performed: liquid chromatography tandem mass spectrometry (LC-MS/MS), urine organic acids, and quantitative acylcarnitine profile. C4 carnitine was elevated as 0.91; urine organic acid analysis showed elevated ethylmalonic acid as 62.87 nmol/molCr (normal, <6.5), methylsuccinate 6.81 nmol/molCr (normal, not detected). Sequence analysis of ACADS revealed a homozygous missense mutation, c.164C>T (p.Pro55Leu). He is growing well and no episodes of seizures or growth retardation had occurred.