• Journal of Life Science
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• v.22 no.11
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• pp.1456-1462
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• 2012

Sorafenib is a multikinase inhibitor and an oral anticancer drug approved for the treatment of patients with advanced renal cell carcinoma and those with unresectable hepatocellular carcinoma. The purpose of this study was to develop an efficient method of the determination of sorafenib in human plasma using tandem mass spectrometry coupled with liquid chromatography (LC/MS/MS) and validate the method by the guidelines of the Korean Food and Drug Administration (KFDA). Plasma samples ($100{\mu}l$) were added with chlorantraniliprole as an internal standard and then mixed with the 0.1% formic acid-containing extraction solution composed of isopropyl alcohol and ethyl acetate (1:4, v/v). After centrifugation, the supernatant was concentrated at $45^{\circ}C$ under negative pressure and centrifugal force. The residue was reconstituted with a mobile phase and injected into the HPLC instrument using a reverse phase Waters XTerra$^{TM}$ C18 column (particle size $3.5{\mu}m$). Liquid chromatography was carried out within the run time of 5 min using a mobile phase composed of buffer (0.1% formic acid and 10 mM ammonium formate), methanol, and acetonitrile (1:6:3, v/v/v). The analytes were monitored by tandem mass spectrometry in the multiple reaction monitoring method programmed to detect sorafenib at 'm/z 465.2 ${\rightarrow}$ 252.5' and chlorantraniliprole at 'm/z 484.4 ${\rightarrow}$ 286.2' with positive electrospray ionization mode ($ES^+$). The result showed the proper linearity ($r^2$ > 0.99) over the range of 2,000-5,000 ng/ml with good accuracy (90.7-103.9%) and precision (less than 10%). The newly developed method using LC/MS/MS was validated by the guideline of KFDA and identified as more sensitive compared to the previous methods.

• The Journal of Korean Academy of Prosthodontics
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• v.52 no.3
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• pp.195-201
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• 2014

Purpose: This study was designed to compare the amount of polymerization shrinkage of dual-cure resin cements according to different polymerization modes and to determine the effect of light activation on the degree of polymerization. Materials and methods: Four kinds of dual-cure resin cements were investigated: Smartcem 2, Panavia F 2.0, Clearfil SA Luting and Zirconite. Each material was tested in three different polymerization modes: self-polymerization only, immediate light polymerization and 5 minutes-delayed light polymerization. The time-dependent polymerization shrinkage-strain was evaluated for 30 minutes by Bonded-disk method at $37^{\circ}C$. Five recordings of each material with three different modes were taken. Data were analyzed using one-way ANOVA and multiple comparison Scheffe′test (${\alpha}$=.05). Results: All materials, except Panavia F 2.0, exhibited the highest polymerization shrinkage-strain through delayed light-activated polymerization. No significant difference between light activation modes was found with Panavia F 2.0. All materials exhibited more than 90% of polymerization rate in the immediate or delayed light activated group within 10 minutes. Conclusion: As a clinical implication of this study, the application of delayed light activation mode to dual-cure resin cements is advantageous in terms of degree of polymerization.

• Korean Journal of Clinical Pharmacy
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• v.16 no.1
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• pp.23-27
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• 2006

Doxorubicin (DXR) is a type of anti-cancer drug called an 'anthracycline glycoside', It works by impairing DNA synthesis, a crucial feature of cell division, and thus is able to target rapidly dividing cells. Doxorubicin is a very serious anti-cancer medication with definite potential to do great harm as well as great good. A liquid chromatography-tandem mass spectroscopy (LC-MS/MS) method was developed to identify and quantify DXR in small-volume biological samples. After the addition of internal standard (IS, $5{\mu}L\;of\;1{\mu}M/ml$ daunorubicin methanol solution) into the serum sample, the drug and IS were extracted by methanol. Following vortex for a 1min and centrifugation at 15,000g for 10 min the organic phase was transferred and evaporated under a vacuum. The residue was reconstituted with $350{\mu}L$ of mobile phase and $10{\mu}L$ was injected into C18 column with mobile phase composed of 0.05M ammonium acetate (0.1 M acetic acid adjusted to pH 3.5) and acetonitrile (40:60, v/v). The flow rate was kept constant at $350{\mu}L/min$. The ions were quantified in the multiple reaction mode (MRM), using positive ions, on a triple quadrupole mass spectrometer. The lower limits of quantification for Doxorubicin in plasma and small tissues were approximately 0.5 ng/mL and 0.5 ng/mL respectively. Intra- and inter-assay accuracy (% of nominal concentration) and precision (% CV) for all analytes were within 15%, respectively.

• The Journal of Korean Institute of Electromagnetic Engineering and Science
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• v.21 no.12
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• pp.1343-1351
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• 2010

In this paper, a novel patch antenna based on the metamaterial CRLH(Composite Right- and Left-Handed) structure is designed, implemented, and measured. Contrary to the standard microstrip patch's fundamental resonance mode of half-wavelength or its positive multiple, the proposed antenna shows the in-phase electric field over the entire antenna. The proposed antenna has a desired omni-directional field pattern which is typical characteristic of $\lambda/4$ monopole antenna, and also shows the merit of low profile. HFSS(High Frequency Structure Simulator) of Ansoft which is based on the FEM(Finite Element Method) is used to simulate the proposed antenna. FR-4 substrate of thickness 1.6 mm and relative permitivity 4.4 is used for the proposed antenna implementation. The implemented antenna showed VSWR (Voltage Standarding Wave Ratio)$\leq$2 for the frequency band from 2.63 GHz to 2.655 GHz which is used for S-DMB (Satellite-Digital Multimedia Broadcasting) service. And measured peak gain and efficiency are 2.65 dBi and 81.14 %, respectively.

• Journal of Pharmaceutical Investigation
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• v.38 no.2
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• pp.135-142
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• 2008

The present study describes the evaluation of the bioequivalence of two atorvastatin tablets, Lipitor $Tablet^{(R)}$ (Pfizer, reference drug) and Atorva $Tablet^{(R)}$ (Yuhan, test drug), according to the guidelines of Korea Food and Drug Administration (KFDA). Forty-nine healthy male Korean volunteers received each medicine at the atorvastatin dose of 40 mg in a $2{\times}2$ crossover study with a two weeks washout interval. After drug administration, serial blood samples were collected at a specific time interval from 0-48 hours. The plasma atorvastatin concentrations were monitored by an high performance liquid chromatography -tandem mass spectrometer (LC-MS/MS) employing electrospray ionization technique and operating in multiple reaction monitoring (MRM) and positive ion mode. The total chromatographic run time was 4.5 min and calibration curves were linear over the concentration range of 0.1-100 ng/mL for atorvastatin. The method was validated for selectivity, sensitivity, linearity, accuracy and precision. $AUC_t$ (the area under the plasma concentration-time curve from time zero to 48hr) was calculated by the linear log trapezoidal rule method. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were complied trom 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 Atorva $Tablet^{(R)}$ / Lipitor $Tablet^{(R)}$ were ${\log}\;0.9413{\sim}{\log}\;1.0179$ and ${\log}\;0.831{\sim}{\log}\;1.0569$, respectively. These values were within the acceptable bioequivalence intervals of ${\log}\;0.8{\sim}{\log}\;1.25$. Based on these statistical considerations, it was concluded that the test drug, Atorva $Tablet^{(R)}$ was bioequivalent to the reference drug, Lipitor $Tablet^{(R)}$.

• Journal of Food Hygiene and Safety
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• v.29 no.2
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• pp.131-140
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• 2014

The objective of this study was to develop a simultaneous method of 8 penicillin antibiotics including amoxicillin, ampicillin, cloxacillin, dicloxacillin, nafcillin, oxacillin, penicillin G and penicillin V in meat using LC-MS/MS. The procedure involves solid phase extraction with HLB cartridge and subsequent analysis by LC-MS/MS. To optimize MS analytical condition of 8 compounds, each parameter was established by multiple reaction monitoring in positive ion mode. The chromatographic separation was achieved on a $C_{18}$ column with a mobile phase of 0.05% formic acid and 0.05% formic acid in acetonitrile at a flow rate of 0.2 mL/min for 20 min with a gradient elution. The developed method was validated for specificity, linearity, accuracy and precision in beef, pork and chicken. The recoveries were 71.0~106%, and relative standard deviations (RSD) were 4.0~11.2%. The limit of detection (LOD) and the limit of quantification (LOQ) were 0.003~0.008 mg/kg and 0.01~0.03 mg/kg, respectively, that are below maximum residue limit (MRL) of the penicillins. This study also performed survey of residual penicillin antibiotics for 193 samples of beef, pork and chicken collected from 9 cities in Korea. Penicillins were not found in all the samples except a sample of pork which contained cloxacillin (concentration of 0.08 mg/kg) below the MRL (0.3 mg/kg).

• Analytical Science and Technology
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• v.29 no.2
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• pp.94-103
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• 2016

An analytical method was developed to determine the amount of spinetoram (spinetoram J and spinetoram L) in livestock samples. The spinetoram was extracted with acetonitrile and purified through a primary secondary amine (PSA) sorbent. The spinetoram residues were then quantified and confirmed using a liquid chromatography–tandem mass spectrometer (LC-MS/MS) in the positive ion mode using multiple reactions monitoring (MRM). Matrix-matched calibration curves were linear over the calibration ranges (0.005-0.5 mg/kg) into a blank extract with r² > 0.994. The limits of detection and quantification were 0.002 and 0.01 mg/kg, respectively. The recovery results of spinetram ranged between 81.9-106.4% at different concentration levels (LOQ, 10LOQ, 50LOQ, n=5) with relative standard deviations (RSDs) less than 10%. All values were consistent with the criteria ranges requested in the Codex guidelines (CAC/GL40, 2003). An interlaboratory study was conducted to validate the method. The proposed analytical method proved to be accurate, effective, and sensitive for spinetoram determination. The method will be used as an official analytical method in Korea.

• Analytical Science and Technology
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• v.24 no.5
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• pp.345-351
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• 2011

A liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI/MS/MS) method was developed and validated for the determination of finasteride in human serum. Beclomethasone was used as internal standard (IS) and liquid-liquid extraction (LLE) using methyl tert-butyl ether (MTBE) was carried out to isolate analyte. The mass transitions monitored in multiple reaction monitoring (MRM) in positive ion mode were m/z 373.2${\rightarrow}$305.2 for finasteride and m/z 409.3${\rightarrow}$391.2 for IS. Retention times of finasteride and IS were 5.81 and 5.46 min, respectively. The limit of quantitation (LOQ) was 0.1 ng/mL and the calibration curve showed good linearity in the range of 0.1~20.0 ng/mL ($R^2$=0.9997). The intra-day assay precision and accuracy were in the range 6.3~10.6% and 97.3~103.6%, respectively, and the inter-day assay precision and accuracy were in the range 0.8~5.2% and 99.8~102.5%, respectively. The sample extract recovery of the method was 80~83%.

• Journal of Food Hygiene and Safety
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• v.33 no.4
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• pp.296-305
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• 2018

Spiroxamine, one of fungicides, is used to control powdery mildew in various crops and black yellow sigatoka in bananas. The major strength of spiroxamine is to control powdery mildew in various crops and bananas yellow sigatoka in bananas. The compound has shown a high level of activity, good persistence and crop tolerance. Besides powdery mildew, good control of rust, net blotch and Rhynchosporium diseases been indicated in cereals, together with a complementary activity against Septoria diseases. In 2017, the maximum residue limit (MRL) of spiroxamine established in Korea. According to Ministry of ood and rug afety) regulations, spiroxamine residues defined only parent compound. Thus, a analytical method is needed to estimate the residue level of the parent compound. The objective of this study was to develop and validate analytical method for spiroxamine in representative agricultural commodities. Samples were extracted with acetonitrile and partitioned with dichloromethane to remove the interfering substances. The analyte were quantified and confirmed liquid chromatograph-tandem mass spectrometer (LC-MS/MS) in positive-ion mode using multiple reaction monitoring (MRM). Matrix matched calibration curves were linear over the calibration ranges ($0.0005{\sim}0.1{\mu}g/mL$) for the analyte in blank extract with coefficient of determination ($r^2$) > 0.99. For validation purposes, recovery studies will be carried out at three different concentration levels (LOQ, 10LOQ, and 50LOQ) performing five replicates at each level. The recoveries 70.6~104.6% with relative standard deviations (RSDs) less than 10%. All values were consistent with the criteria ranges in the Codex guidelines (CAC/GL40, 2003) and MFDS guidelines. proposed analytical method be used as an official analytical method in the Republic of Korea.

• Korean Journal of Biological Psychiatry
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• v.10 no.1
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• pp.70-79
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• 2003

Object : Currently, the alteration of cytokine system has been known to play an important role in regard to depressive symptom. We focused on the relationship between immunological parameters and clinical improvement in major depressive disorder. Method : Data were collected on 26 patients with major depressive disorder using a 8-week prospective follow-up design. After 8-week treatment period with fluoxetine, patients were classified into a response group and a non-response group according to their psychopathological outcome as evaluated by Hamilton Depression Rating Scale. The differences of the immunological parameters between pre-treatment phase and post-treatment phase were compared among patients. The difference of those was also compared within each phase among them. The relationship between socio-demographic variables, depression, cytokine, mononuclear cells was examined by correlation analysis. Multiple regression analyses were performed to explore the predictors of clinical improvement of major depressive disorder. Result : Pre-treatment levels of IL-$1{\beta}$ in the response group were significantly higher than those in the non-response group. Pre-treatment levels of IL-$1{\beta}$ of all patients and in the response group were positively correlated with pre-treatment monocyte counts. Patients with subsequent remission showed significantly lower IL-6 values at baseline than those with non-response. Post-treatment values of IL-6 did not differ significantly among the patients. The correlation test showed more frequent relations among cytokines and mononuclear cells in the response group than in the non-responder group. Especially, serum level of IL-6 in pre-treatment phase was only significantly correlated with HAMD score after 8-week treatement phase, while other cytokines and mononuclear cells were not. Pretreatment level of IL-6 was of paramount importance in predicting clinical improvement of depressive symptom. Conclusion : The immune system of major depressive disorder patients might dichotomize the patients into subsequent responders and non-responders. Immune system might be of great influence on the clinical improvement of major depressive disorder. The mode of interaction between depression and cellular immune function and the mediators responsible for the cytokine production need to be studied further.