• Proceedings of the Korean Society of Toxicology Conference
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• 2006.11a
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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.

• Food Science of Animal Resources
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• v.22 no.4
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• pp.352-357
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• 2002

Antimutagenic effects of extracts from curry powder and its individual fourteen kinds of spices, were investigated by Ames test. The antimutagenic effects against a direct mutagen, 2-nitrofluorene(2 -NF) and two indirect mutagens, 2-anthramine(2-AT) and 2-acetamidofluorene (2-AE) in the S. typhimurium TA98 were tested. For the 2-NF, the antimutagenicity of cinnamon, fenugreek, fennel, ginger, clove, turmeric and celery seed were determined as 42, 38, 32, 28, 24, 23 and 20%, respectively. The antimutagenicity of clove against the 2-AT was the highest (116%), and followed by the order of celery seed(103%), cardamon(100%), red pepper(99%), cinnamon(92%), cumin(83%), ginger(82%), fennel(82%), coriander (71%), nutmeg(68%) and turmeric (55%). The results also showed that the antimutagenic effect of clove against the 2-AF was superior to other spices. In case of curry powder among more than 10 kinds of spices, the antimutagenenicity against the 2-AT and 2-AF showed 23% and 6%, respectively, but no effect was observed against the 2-NF.

• Korean Journal of Food Science and Technology
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• v.28 no.6
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• pp.1059-1064
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• 1996

The inhibitory effects of chitosan on mutagenicity induced by 3-amino-1-methyl-5H-pyrido [4,3-b] indole (Trp-P-2), sodium azide (SA), 2-nitrofluorene (2-NF), and 4-nitroquinoline oxide (4-NQO) were investigated using Salmonella typhimurium reversion assay and SOS Chromotest. In Salmonella typhimurium reversion assay. Chitosan showed 24-65% of inhibitory effect against the mutagenicity of an indirect-acting mutagen, Trp-P-2. On the other hand, no inhibitory effect was observed against the mutagenicity of direct-acting mutagens (2-NF, SA). In SOS chromotest. chitosan showed 46-49% effects on SOS function induced by 4-NQO. Chitosan inhibited the mutagenicity induced by Trp-P-2 with 9-39% of inhibition rate. It was also evaluated whether inhibitory effect of chitosan is due to its bio-antimutagenic or desmutagenic action. Chitosan at high concentrations showed a bio-antimutagenicity with dose-dependent manner, but it showed a desmutagenicity at low concentrations against the mutation induced by Trp-P-2.

• Korean Journal of Food Science and Technology
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• v.30 no.3
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• pp.688-692
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• 1998

To detect naturally occuring antimutagenic substances from wild mushrooms in Korea, the screening for the antimutagenic compounds containing in ethanol and water extracts of 13 wild mushrooms toward benzo(a) pyrene (B(a)P) and $N-methyl-N'-nitro-N-nitrosoguanidine\;(MNNG)$ using the Ames assay system with Salmonella typhimurium TA98 and TA100 were studied. The ethanol extracts of Polyporus dispansus, Cantharellus infundibuliformis, Agaricus subrutilescens, Daedalea dickinsii, Panaeolus papilionaceus and Hydnum repandum showed significantly antimutagenic activity toward B(a)P. The water extracts of Hydnum repandum showed the strong antimutagenic activity toward B(a)P in S. typhimurium TA100, however the water extracts of the mushrooms did not show antimutagenic activity. Whereas 5 out of 13 samples exhibited antimutagenicity toward a direct mutagen of MNNG. The water extracts from mushrooms also not showed antimutagenic activity. The antimutagenic effect increased with increasing concentraion of the ethanol extracts from Polyporus dispansus.

• KOREAN JOURNAL OF CROP SCIENCE
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• v.52 no.3
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• pp.303-310
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• 2007

Sweetpotato shoot tops (leaves, tips and petioles) are known to be very useful parts as vegetables because of their high nutritive values and great biomass yield. In this study, the phenolic compound contents, antibacterial activity, mutagenic activity, and antimutagenic activity were investigated in sweetpotato tips that were 10-15cm of shoot top including stems, petioles and tender leaves after sprout of storage roots. The study was done by extracting sweetpotato tips with 80% ethanol and the ethanol fraction was re-extracted with hexane, chloroform, ethyl acetate, butanol and water. In ethyl acetate and butanol fractions, total phenolic compounds contained 95. 6mg/g extract and 69.3 mg/g extract, respectively, The antibacterial activity was measured using the paper disk method with concentrations of 1, 2, 5 and 10 mg/disk of butanol and ethyl acetate fractions against L. monocytogenes and S. Typhimurium strains. Higher doses of solvent extracts showed the higher antibacterial activities. In addition, 5, 10 and 20 mg/mL of the extracts were tested to determine the antibacterial activity in liquid culture. The sweetpotato leaf extract by ethyl acetate showed 1 log reduction compared to control after 24 hrs on Listeria monocytogenes, but 20 mg/ml of butanol extract completely inhibited the growth of the pathogen after 12 hrs. The extracts from ethyl acetate or butanol on Salmonella Typhimurium did less than 1 log reduction during cultivation compared to control. The numbers of S. Typhimirium TA98 and TA100 revertant colonies were 29-33 and 159-188 CFU/plate, respectively, indicating that solvent extracts were no mutagenic activity. The antimutagenic test was performed by adding direct mutagen 2-NF and MMS, and butanol and ethyl acetate showed antimutagenic effect. Thus, this study showed that sweetpotato tips had high phenolic contents and both antimicrobiol and antimutagenic properties. Sweetpotato tips would be good nutritive source because of their high nutrient content without any toxicity in consuming.