Korea Food And Drug Administration Research Articles

Comparison of Medical Device Regulations in India, Japan and South Korea

Increased health awareness, a growing middle class, and government health efforts are projected to propel India's medical equipment market forward in the next years. With the publication of the Medical Device Rules in 2017, Indian authorities revised the medical device regulatory process. The devices included in the link are currently regulated medical devices and in vitro diagnostic devices, as well as their classifications. CLA (Central Licensing Authority) is in charge of all import device licencing, as well as manufacturing, loan, and wholesale licences for Class C and Class D medical devices.
 Because of its complicated registration process and linguistic obstacles, Japan is regarded one of the most difficult markets for overseas medical device producers. The Pharmaceutical and Medical Device Agency, which works in tandem with the MHLW (Ministry of Health and Labour Welfare), is in charge of reviewing drug and medical device applications in Japan. The Pharmaceuticals and Medical Devices Act is a federal law that regulates the sale of pharmaceuticals and medical devices. The Pharmaceuticals and Medical Devices Act, also known as the Act on Securing Quality, Efficacy, and Safety of Pharmaceuticals, Medical Devices, Regenerative and Cellular Therapy Products, Gene Therapy Products, and Cosmetics, lays out the current PMDA (Pharmaceuticals and Medical devices Agency) laws in Japan.
 South Korea is one of the largest health-care markets in the Asia-Pacific region. Medical Devices in South Korea are regulated by the Ministry of Food and Drug Safety (MFDS), formerly known as the Korea Food and Drug Administration (KFDA). Medical Devices in South Korea are regulated by the Ministry of Food and Drug Safety, formerly known as the Korea Food and Drug Administration. The Medical Device Act of 2015 governs current medical device laws in Korea. To access the South Korean Medical-Device-Market, you must first obtain marketing approval from the local Medical Device Authority, the Medical Device Information & Technology Centre, which is part of the Ministry of Food and Drug Safety. With the MFDS notification No. 2020-29, the South Korean Ministry of Food and Drug Safety launched UDI (Unique Device Identification System) operations in 2018. Article 20 of the Medical Device Act and Article 54-2 of the Medical Device Act Enforcement Regulations make UDI compliance mandatory.

Viscosity Measurement of Whole Blood with Parallel Plate Rheometers

There are many factors that affect the increase or decrease of viscosity of the whole blood. Because of this, measuring the viscosity of whole blood is difficult to correlate with specific etiologies, so it tends to disregard the information on blood viscosity. This study is to find out the characteristics of the method of measuring the viscosity of whole blood using the parallel plate method, which is officially registered as a medical device with the approval of the Korea Food and Drug Administration (KFDA), and to apply it to the measurement of whole blood viscosity. The accuracy of the parallel plate measurement is verified by comparing with the measurement results using the commercially available scanning capillary method. In addition, statistically meaningful results are obtained between the viscosity and some components of the whole blood. It is expected that the research will be carried out to understand the correlation between the viscosity of whole blood and specific components of blood and to identify the prognostic signs of etiology in certain diseases, especially in cardiovascular and cerebral vessels diseases.

Comparison of Bone Marrow Aspirate Concentrate and Allogenic Human Umbilical Cord Blood Derived Mesenchymal Stem Cell Implantation on Chondral Defect of Knee: Assessment of Clinical and Magnetic Resonance Imaging Outcomes at 2-Year Follow-Up

Biological repair of cartilage lesions remains a significant clinical challenge. A wide variety of methods involving mesenchymal stem cells (MSCs) have been introduced. Because of the limitation of the results, most of the treatment methods have not yet been approved by the Food and Drug Administration (FDA). However, bone marrow aspirate concentrate (BMAC) and human umbilical cord blood derived mesenchymal stem cells (hUCB-MSCs) implantation were approved by Korea FDA. The aim of this study was to evaluate clinical and magnetic resonance imaging (MRI) outcomes after two different types of MSCs implantation in knee osteoarthritis. Fifty-two patients (52 knees) who underwent cartilage repair surgery using the BMAC (25 knees) and hUCB-MSCs (27 knees) were retrospectively evaluated for 2 years after surgery. Clinical outcomes were evaluated according to the score of visual analogue scale (VAS), the International Knee Documentation Committee (IKDC) subjective, and the Knee Injury and Osteoarthritis Outcome Score (KOOS). Cartilage repair was assessed according to the modified Magnetic Resonance Observation of Cartilage Repair Tissue (M-MOCART) score and the International Cartilage Repair Society (ICRS) cartilage repair scoring system. At 2-year follow-up, clinical outcomes including VAS, IKDC, and KOOS significantly improved (P < 0.05) in both groups; however, there were no differences between two groups. There was no significant difference in M-MOCART [1-year (P = 0.261), 2-year (P = 0.351)] and ICRS repair score (P = 0.655) between two groups. Both groups showed satisfactory clinical and MRI outcomes. Implantation of MSCs from BMAC or hUCB-MSCs is safe and effective for repairing cartilage lesion. However, large cases and a well-controlled prospective design with long-term follow-up studies are needed.

(±)-Kituramides A and B, pairs of enantiomeric dopamine dimers from the two-spotted cricket Gryllus bimaculatus

Two-spotted cricket Gryllus bimaculatus is one of many cricket species, and it is widely used as a food source for insectivorous animals. Moreover, this species is one of the edible insects approved by the Korea Food and Drug Administration (KFDA). (±)-Kituramides A (1) and B (2), which are pairs of novel enantiomeric dopamine dimers possessing a formamide group, were isolated from the two-spotted cricket, together with four other known biosynthetically related compounds (3-6). The chemical structures of 1 and 2 were elucidated using a combination of 1D and 2D NMR spectroscopic experiments and HR-ESIMS data. Compounds 1 and 2 were identified as racemic mixtures; the enantiomers (+)-1/2 and (-)-1/2 were successfully separated by utilizing a chiral HPLC column. The absolute configurations of (±)-1 and (±)-2 were unambiguously delineated by the application of quantum chemical ECD calculations. Further, these insect-derived substances were evaluated to understand their effects on cytokine expression in adipocytes. Treatment with (-)-1, (+)-2, and (-)-2 during adipocyte differentiation significantly promoted the expression of Leptin and IL-6, which resembles the actions of dopamine.

Translational status of biomedical Mg devices in China

Magnesium (Mg) and its alloys as temporary medical implants with biodegradable and properly mechanical properties have been investigated for a long time. There are already three kinds of biodegradable Mg implants which are approved by Conformite Europeene (CE) or Korea Food and Drug Administration (KFDA), but not China Food and Drug Administration (CFDA, now it is National Medical Products Administration, NMPA). As we know, Chinese researchers, surgeons, and entrepreneurs have tried a lot to research and develop biodegradable Mg implants which might become other new approved implants for clinical applications. So in this review, we present the representative Mg implants of three categories, orthopedic implants, surgical implants, and intervention implants and provide an overview of current achievement in China from academic publications and Chinese patents. We would like to provide a systematic way to translate Mg and its alloy implants from experiment designs to clinical products.

Quantitative Analysis of Metal Contents in Korean Herbs and Herbal Products to Give Advice for Metal Allergic Patient.

BackgroundHerbs have been used worldwide as complementary and alternative medicines. In Korea, herbs for medical purpose are strictly controlled by the Korea Food and Drug Administration (KFDA). But it does not provide standards for metal antigens.ObjectiveThis study conducted to identify the metal contents of Korean herbs and herbal products and to give information on counselling metal allergic patient.MethodsThe concentration of three metal allergens with high antigenicity, cobalt (Co), chromium (Cr), nickel (Ni) was quantitatively determined using inductively coupled plasma with a mass spectrometer after nitric acid (HNO3) digestion. The herbal objects are as follows: 1) ten kinds of herb plants, 2) ten herbal products sold in Korean drugstores, and 3) ten herbal extracts prescribed by Korean herbal doctors.ResultsIn 30 samples, Ni and Cr were detected in all items. Co was not detected in two drugstore products.ConclusionAlthough the levels of metal detected in this study were very low relative to international guidelines and KFDA regulations, the herbal preparations contained similar or higher metal levels than known metal-rich foods. It can cause problems when it added to the daily diet and cause deterioration of skin lesions of metal sensitized person.

Fully validated SRM-MS-based method for absolute quantification of PIVKA-II in human serum: Clinical applications for patients with HCC

Protein induced by vitamin K absence or antagonist-II (PIVKA-II), an abnormal form of prothrombin, is used as a serological biomarker that aids in the diagnosis of hepatocellular carcinoma (HCC). PIVKA-II is typically measured by liquid binding assay (LiBA). However, without an internal standard, it is difficult to obtain accurate results. Thus, we aimed to develop a selected reaction monitoring-mass spectrometry (SRM-MS)-based assay to quantify PIVKA-II in serum. Our SRM-MS assay entailed the addition of a protein analog as an internal standard, the enrichment of PIVKA-II using a monoclonal antibody, chymotrypsin digestion, online desalting, and SRM-MS analysis. The performance of the SRM-MS assay was compared with that of LiBA in 400 human serum samples (100 chronic hepatitis, 100 liver cirrhosis, and 200 HCC). Integrated multinational guidelines were followed to validate the assay for clinical implementation. The linearity ranged from 1.28 to 100,000 ng/mL, and the use of a labeled protein analog as an internal standard allowed the error from the sample preparation to be corrected, improving the precision and accuracy. The SRM-MS assay was validated to meet all of the criteria of the compliance with guidelines per the US Food and Drug Administration (FDA), European medicines agency (EMA), Korea FDA (KFDA), and Clinical & Laboratory Standards Institute (CLSI). We have developed and validated a robust and reproducible SRM-MS assay that is superior to the conventional method of distinguishing HCC from noncancer patients, based on PIVKA-II levels, and satisfies clinical standards. This method has potential applications in quantifying other protein biomarkers.

Case Study of Genetic Analysis for Detection of Pork Mixed in Beef Jerky

본 실험에서는 식품의약품안전평가원의 식품 중 사용원료 진위 판별 지침서에 명시 되어있는 소와 돼지에 대한 primer를 이용한 PCR 반응의 민감도와, 새롭게 선별한 primer의 PCR 민감도를 비교하였다. 새로운 primer의 타겟 부위는 cytochrome b이다. Primer의 적합성을 확인하기 위해 돼지고기와 소고기를 이용하여 DNA를 추출 후 PCR을 통하여 확인 하였다. 육포시료에서 식품의약품안전평가원의 식품 중 사용원료 진위 판별 지침서에 명시 되어있는 소에 대한 primer를 사용하였을 경우, PCR 산물을 얻을 수 있었음에 반해, 돼지 primer를 이용하였을 때는 PCR 산물을 얻을 수 없었다. 반면에 새로설정 한 primer에서는 전체 27개의 육포시료 중 13개에서 돼지 primer를 이용한 PCR 산물을 얻을 수 있었다. 이렇게 얻은 PCR 산물을 시퀀싱을 통하여 확인 해본 결과, 돼지 (Sus scrofa)임을 확인 할 수 있었다. 그러므로 본 실험에 사용 한 육포시료 중 일부는 돼지와 소고기의 혼합물임을 확인 할 수 있었다.We compared the sensitivity of polymerase chain reaction (PCR) using newly discovered bovine and porcine primers to previously reported primers of the Korea Food and Drug Administration (KFDA). The target site for the new primers was cytochrome b. The suitability of the primers was confirmed by conducting PCR on DNA extracted from beef and pork control. When the beef jerky samples were tested by PCR with the conventional primers of the KFDA, the DNA was successfully amplified from all samples with the bovine primer, whereas no PCR products were obtained with the porcine primer. By contrast, in the experiments with the new primers, we obtained PCR products from 13 of 27 beef jerky samples using the porcine primer. We have confirmed that the base sequences of these 13 samples match to the sequence of pigs (Sus scrofa) in the National Center for Biological Information (NCBI) database. Therefore, we determined that some of the beef jerky samples we received are mixture of beef and pork.

간편한 DNPH 유도체화 HPLC 분석법을 이용한 화장품 중 포름알데하이드 분석

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(pH5.0)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 0.2ppm과 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.

Toxic metal content in 52 frequently prescribed herbal medicines on the Korean market

This study was conducted to investigate the toxic metal content (Pb, As, Cd and Hg) of 52 frequently prescribed herbal medicines and to identify herbal medicines that exceed the Korea Food and Drug Administration (KFDA) maximum limits. A total of 3534 samples, including 1966 domestic samples and 1568 imported samples, were analysed using an Inductively Coupled Plasma-Mass Spectrometer (ICP-MS). Total amounts of Pb, As, Cd and Hg were significantly different between domestic (0.63 mg kg−1) and imported (0.81 mg kg−1) medicines (p < 0.05). Among the 52 kinds of samples, 4 kinds of herbs required quality control for Pb and 12 kinds of herbs required quality control for Cd. No sample contained As and Hg above the limits.

Current Status and Challenges of Cancer Clinical Trials in Korea.

PurposeCancer clinical trials in Korea have rapidly progressed in terms of quantity and quality during the last decade. This study evaluates the current status of cancer clinical trials in Korea and their associated problems.Materials and MethodsWe analyzed the clinical trials approved by the Korea Food and Drug Administration (KFDA) between 2007 and 2013. A nationwide on-line survey containing 22 questions was also performed with several cooperative study groups and individual researchers in 56 academic hospitals.ResultsThe number of cancer clinical trials approved by the KFDA increased almost twofold from 2007 to 2013. The number of sponsor-initiated clinical trials (SITs) increased by 50% and investigator-initiated clinical trials (IITs) increased by almost 640%. Three hundred and forty-four clinical trials were approved by the KFDA between 2012 and 2013. At the time of the on-line survey (August 2013), 646 SITs and 519 IITs were ongoing in all hospitals. Six high volume hospitals were each conducting more than 50 clinical trials, including both SITs and IITs. Fifty-six investigators (31%) complained of the difficulties in raising funds to conduct clinical trials.ConclusionThe number of cancer clinical trials in Korea rapidly increased from 2007 to 2013, as has the number of multicenter clinical trials and IITs run by cooperative study groups. Limited funding for IIT is a serious problem, and more financial support is needed both from government agencies and public donations from non-profit organizations.

Dietary folate intake and food sources of children and adolescents in Chungcheong area - Using nutrient database revised by measured folate in selected foods

Purpose: The purpose of this study was to estimate dietary folate intake and food sources of children and adolescents using a nutrient database revised based on measured folate in selected foods. Methods: Folate content in 51 foods known as folate sources was measured by microbiological assay after trienzyme extraction. Folate intake was estimated from a part of the data of ‘Dietary Intake Survey of Infants, Children and Adolescents in 2007~2008’ conducted by the Korea Food and Drug Administration (KFDA) and the Korea Health Industry Development Institute (KHIDI). The study subjects were 567 children aged 1~19 years living in the Chungcheong area who completed two 24-hour recalls. Results: Folate values were revised by replacing the values in the current database with the analyzed values except when the value in the current database was between the analytical values or was not different from the mean analytical value by more than 10%. Among the revised values of 40 food items, folate values of 36 foods were lower than the current values. Mean folate intakes estimated with the revised database were approximately 70~80% lower than those estimated with the current database. Mean folate intakes of males aged 12~14 and females aged 12~19 were lower than the 2010 Recommended Nutrient Intakes (RNIs). Chicken's eggs, Kimchi, rice, mandarin, and laver were found to be main food sources of folate. Conclusion: In this study, mean dietary folate intakes were lower than those estimated with the current database. Further analyses for folate content especially in cooked foods commonly consumed in Korea are needed using a reliable assay in order to accurately assess folate intake of the Korean population. In addition, nutrition education should be provided for adolescent females in order to increase consumption of folate-rich foods.

Dietary folate intake and food sources of children and adolescents in Chungcheong area - Using nutrient database revised by measured folate in selected foods

Purpose: The purpose of this study was to estimate dietary folate intake and food sources of children and adolescents using a nutrient database revised based on measured folate in selected foods. Methods: Folate content in 51 foods known as folate sources was measured by microbiological assay after trienzyme extraction. Folate intake was estimated from a part of the data of ‘Dietary Intake Survey of Infants, Children and Adolescents in 2007~2008’ conducted by the Korea Food and Drug Administration (KFDA) and the Korea Health Industry Development Institute (KHIDI). The study subjects were 567 children aged 1~19 years living in the Chungcheong area who completed two 24-hour recalls. Results: Folate values were revised by replacing the values in the current database with the analyzed values except when the value in the current database was between the analytical values or was not different from the mean analytical value by more than 10%. Among the revised values of 40 food items, folate values of 36 foods were lower than the current values. Mean folate intakes estimated with the revised database were approximately 70~80% lower than those estimated with the current database. Mean folate intakes of males aged 12~14 and females aged 12~19 were lower than the 2010 Recommended Nutrient Intakes (RNIs). Chicken's eggs, Kimchi, rice, mandarin, and laver were found to be main food sources of folate. Conclusion: In this study, mean dietary folate intakes were lower than those estimated with the current database. Further analyses for folate content especially in cooked foods commonly consumed in Korea are needed using a reliable assay in order to accurately assess folate intake of the Korean population. In addition, nutrition education should be provided for adolescent females in order to increase consumption of folate-rich foods.

Simultaneous multi-determination and transfer of eight pesticide residues from green tea leaves to infusion using gas chromatography

A method for determining eight pesticide (cyhalothrin, flufenoxuron, fenitrothion, EPN, bifenthrin, difenoconazole, triflumizole, and azoxystrobin) residues in made green tea as well as a tea infusion (under various brewing water temperatures; 60, 80, and 100°C) using gas chromatography (GC) micro-electron capture detector (μECD) was developed and validated. The extraction method adopted the relatively commonly used approach of solid sample hydration, with the green tea hydrated before being extracted through salting out with acetonitrile followed by a cleanup procedure. The analytes were confirmed using GC-coupled to tandem mass spectrometry (GC/MS/MS) with a triple quadrupole. The linearity of the calibration curves yielded determination coefficients (R2) >0.995. Recoveries were carried out using blank samples spiked with all analytes at two levels. The results demonstrated that all pesticides were recovered within the range of 77–116% with a relative standard deviation (RSD) ⩽14%. The quantification limits of 0.015–0.03mg/kg were lower than the maximum residue limits (MRLs) set by the Korea Food and Drug Administration (KFDA) for all analytes (0.05–10mg/kg). The infusion study indicated that cyhalothrin, flufenoxuron, and bifenthrin did not infuse into the tea brew from the made tea. Increases in brewing time resulted in increased transfer of azoxystrobin, fenitrothion, and difenoconazole from the made tea to the brew; however, this was not the case with triflumizole or EPN. We conclude that transfer of pesticides appeared to be dependent on their water solubilities and drinking a cup of tea is recommended to be at a water temperature of 60°C.

Single-Dose Oral Toxicity Test of Woohwangchungshim-won in Mice

The object of this study was to obtain acute toxicity information (single-dose oral toxicity) of Woohwangchungshim-won (WHCSW), a pill type herbal medicine used in Korean Medicine (KM) for treating stroke. In order to obtain the 50% lethal dose (LD50), approximate lethal dosage (ALD) and target organs, WHCSW powders were once orally administered to female and male ICR mice at dose levels of 2,000, 1,000, 500 and 0 (control) ㎎/㎏ (body weight.) according to the recommendation of Korea Food and Drug Administration (KFDA) Guidelines (Notification No. 2009-116). The mortality and changes in the body weight, clinical signs and gross observation were monitored for 14 days after single-dose oral administration of WHCSW according to KFDA Guidelines with organ weights and histopathological changes were observed in 12 principle organs. After single-dose oral administration of WHCSW, we could not find any mortality and toxicological evidences up to 2,000 ㎎/㎏-administered group, except for some accidental findings and dose-independent increases of body weight gains in female 1,000 and 500 ㎎/㎏ -administered female mice. The results obtained in this study suggest that the LD50 and ALD of WHCSW in both female and male mice after single-dose oral administration were considered as over 2,000 ㎎/㎏ because no mortalities were detected up to 2,000 ㎎/㎏ that was the highest dose recommended by KFDA and Organization for Economic Co-Operation and Development (OECD), and can be safely used in clinics.

Single Oral Dose Toxicity Test of Choweseuncheng-tang, a Polyherbal Formula in ICR Mice

The object of this study was to evaluate the single dose toxicity of Choweseuncheng-tang (CWS), a polyherbal formula have been traditionally used as prevention or treatment agent for various diseases as Tae-eumin prescription on Korean medicinal theory, Sasang-euihak, in male and female mice. Aqueous extracts of CWS (yield = 11.00%) was administered to female and male mice as an oral dose of 2,000, 1,000 and 500 mg/kg (body weight) according to the recommendation of Korea Food and Drug Administration (KFDA) Guidelines. Animals were monitored for the mortality and changes in body weight, clinical signs and gross observation during 14 days after dosing, upon necropsy; organ weight and histopathology of 14 principle organs were also examined. As results, we could not find any CWS treatment related mortality and clinical signs, changes in the body and organ weights, gross findings and changes in histopathology of principle organs, except for some dose-independent accidental findings. The results obtained in this study suggest that the 50% lethal dose and approximate lethal dose of CWS aqueous extracts in both female and male mice were considered as over 2,000 mg/kg, the limited highest dosage recommended by KFDA Guidelines, and can be safety used in clinics.

고추 유과의 저장 중 품질특성 변화 및 유통기한 설정

This study was carried out to investigate the changes in the quality properties of red pepper Yukwa (red pepper liquid fermented with lactic acid bacteria was added to the Yukwa) during the storage period. To determine the shelf life of red pepper Yukwa, the rice Yukwa (control) and red pepper Yukwa were stored at 15, 25, and <TEX>$35^{\circ}C$</TEX> for 70 days. Also, the quality properties of red pepper Yukwa, such as acid value, peroxide value, texture, color, and sensory evaluation were measured. Although the acid value of rice Yukwa and red pepper Yukwa increased during storage, the red pepper Yukwa showed a lower acid value score (1.09mg KOH/g) than that (1.19mg KOH/g) of the rice Yukwa. Nevertheless, these values did not exceed the guideline maximum values of 2.0 g KOH/g specified in the Korean Food Code. The peroxide values of samples had significantly increased after 42 days. Especially, the peroxide value scores for the rice Yukwa and red pepper Yukwa were the highest at 146.49 and 126.79 meq/kg at <TEX>$35^{\circ}C$</TEX>, respectively. Hardness and brittleness in textural properties increased up to 70 days. The sensory values for the red pepper Yukwa for overall acceptance, taste;texture and appearance were the highest. The results indicated that by using the 'Visual Shelf life Simulator for foods' of the Korea Food and Drug Administration (KFDA) the shelf life of red pepper Yukwa is estimated to be 274.78 days.

Hesperidin Suppresses Melanosome Transport by Blocking the Interaction of Rab27A-Melanophilin

We investigated the inhibitory effects of hesperidin on melanogenesis. To find melanosome transport inhibitor from natural products, we collected the structural information of natural products from Korea Food and Drug Administration (KFDA) and performed pharmacophore-based in silico screening for Rab27A and melanophilin (MLPH). Hesperidin did not inhibit melanin production in B16F10 murine melanoma cells stimulated with α-melanocyte stimulating hormone (α-MSH), and also did not affect the catalytic activity of tyrosinase. But, hesperidin inhibited melanosome transport in melanocyte and showed skin lightening effect in pigmented reconstructed epidermis model. Therefore, we suggest that hesperidin is a useful inhibitor of melanosome transport and it might be applied to whitening agent.

A matrix sensitive gas chromatography method for the analysis of pymetrozine in red pepper: Application to dissipation pattern and PHRL

A gas chromatography (GC) method for the analysis of pymetrozine was developed after utilizing matrix enhancement effect of pymetrozine to nitrogen phosphorus detector (NPD). Samples were extracted with acetonitrile and purified through primary secondary amine (PSA) and C18 dispersive sorbent. Matrix-matched calibration curve prepared after spiking standard pymetrozine across the studied range of concentrations (0.003–1.0mg/L) into blank red pepper extract was excellent with a determination coefficients (R2)=1. Recovery studies were carried out at three concentration levels (0.04, 0.4, and 2.0mg/kg, n=3) and the rates were ranged between 77.2% and 109.1%, with relative standard deviations ranged from 1.3% to 16.4%. The developed method was applied to field samples to characterize the dissipation pattern, half life, and pre-harvest residue limits (PHRL). The dissipation rates of the analyte were ascribed to first-order kinetics with half-life of 2.7 and 2.5days for recommended and double the recommended doses. From the PHRL curve, we could predict that if the residue level of pymetrozine is below the 1.23mg/kg at 10days or 0.71mg/kg at 7days before harvest, then the residues will be below the maximum residue limits (MRL=0.2mg/kg) established by the Korea Food and Drug Administration (KFDA).

생물학적 동등성 시험을 위한 2×k 교차설계법의 통계적 고려

The Korea Food and Drug Administration(KFDA) recommends the use of a crossover design to assess the bioequivalence of generic drugs. However, a standard crossover design for bioequivalence trials is often considered problematic due to ethical and economic issues as highly variable drugs are usually required by large numbers of subjects when designing the trial. To overcome this problem a crossover design has been a recommended option as per US regulations; in addition, a crossover design has also recently drawn special attention as an efficient alternative. The current KFDA regulation requires an ANOVA table for every bioequivalence study; however, ANOVA tables of and crossover designs have never been published in the literature. This study shows the derivation of tables of analysis of variance for a cross-over design and a cross-over design. We also suggest a sample size formulas for , and crossover designs to provide information on the selection of efficient designs for highly variable drugs.