• Journal of Food Hygiene and Safety
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• v.33 no.2
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• pp.118-123
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• 2018

The objective of this study was to develop a sensitive method for the identification and determination of nitrovin in fishery products by using a solid-phase extraction (SPE), as performed with a liquid chromatography-tandem mass spectrometry (LC-MS/MS). The samples were extracted with a mixture of acetonitrile and water, and were then defatted with acetonitrile saturated hexane, after which further clean-up was accomplished with SPE on the hydrophilic-lipophilic balance (HLB) cartridges. The analytes were subsequently ionized in the positive mode of an electrospray ionization (ESI), and where thereby detected in a process of multiple reaction monitoring (MRM). The linearity (expressed as correlation coefficients) of the matrix calibration curves was > 0.985. The limit of the quantification for the nitrovin was measured at 0.001 mg/kg. The accuracy (expressed as average recovery) was noted between 72.1 and 122%. The precision (expressed as coefficient variation) was noted from 2.9 to 16.9%. According to the CODEX CAC/GL-71 guideline accuracy, precision, linearity, and limit of detection were determined in three matrices (which were flatfish, eel and shrimp). The proposed method was suitable for analyzing the associated nitrovin residues. This application and result can also be a factor to contribute to the non-detection drugs management in fishery products.

• YAKHAK HOEJI
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• v.57 no.5
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• pp.330-336
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• 2013

"The Act on Medication Treatment of Sexual Impulse of Sex Offenders" known as chemical castration has been effective since July 2011 in Korea. According to the law, monitoring of male sex hormone in urine is enforced to request National Forensic Service more than once a month after injection of medicine designed to reduce sex impulse. We established a rapid and sensitive method for the monitoring of testosterone (T) and epitestosterone (E) in human urine by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Three mL of urine was pretreated by solid-phase extraction for purification and performed enzymatic hydrolysis. The pretreated samples were extracted twice with 2 ml of ethyl acetate and n-hexane (2 : 3). The separation was applied on Thermo Hypersil GOLD C18 column ($1.9{\mu}m$, $100{\times}2.1mm$). A gradient elution of methanol and water of 0.1% formic acid were used as mobile phase and the retention time was less than 10 min. LC-MS/MS system coupled with an electrospray ionization source was performed in multiple reaction monitoring mode. The transitions of the analytes executed as following: m/z $289{\rightarrow}97$, 109 for T and E, m/z $292{\rightarrow}109$ for $T-d_3$ and $E-d_3$ as internal standards. The validation results of the method were satisfactory. The limits of detection were 0.05 ng/ml and the limits of quantification were 0.1 ng/ml. This method was successfully applied to real human urine sample. The developed method will be useful for monitoring T/E ratio in urine of sex offenders.

• Analytical Science and Technology
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• v.25 no.6
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• pp.435-440
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• 2012

A liquid chromatography-electrospray ionization-tandem mass spectrometry method (LC-ESI-MS/MS) was used for determining perchlorate in the Gum-River surface water. Sample was directly injected into LC-ESI-MS/MS after the filtrations using PTFE filter paper. The coefficient of variation of perchlorate was less than 3% and the limit of quantification was 0.17 ${\mu}g/L$. Water samples were collected from thirty-five basins of Gum-River on February, April and June 2012, respectively. As a result, perchlorate was detected in the concentration range of 0.23-3.73 ${\mu}g/L$ (mean 0.20 ${\mu}g/L$) in the frequency of 15% in general surface water and in the concentration range of 0.36-25.10 ${\mu}g/L$ (mean 1.69 ${\mu}g/L$) in the frequency of 36% in surface water samples near industry area.

• Biomolecules & Therapeutics
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• v.16 no.3
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• pp.190-196
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• 2008

Deoxypodophyllotoxin (DPT) is a medicinal herb product isolated from Anthriscus sylvestris. DPT possesses beneficial activities in regulating immediate-type allergic reaction and anti-inflammatory activity through the dual inhibition of cyclooxygenase-2 and 5-lipoxygenase. In the present study, the metabolism of DPT was further characterized in rat liver microsomes isolated from male Sprague Dawley rats. The metabolism of DPT was NADPH-dependent. In addition, when liver microsomes were incubated with SKF-525A, a well-known CYP inhibitor, in the presence of $\beta$-NADPH, the metabolism of DPT was significantly inhibited. Using enriched rat liver microsomes, the anticipated isoforms of cytochrome P450s (CYPs) in the metabolism of DPT were partially characterized. Phenobarbital-induced microsomes increased in the formation of metabolite M1. The metabolite M3 was only produced in the enriched microsomes isolated from dexamethasone-treated rats. The results indicated that the metabolism of DPT would be CYP-dependent and that CYP2B and CYP3A might be important in the metabolism of DPT in rats.

• YAKHAK HOEJI
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• v.57 no.3
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• pp.194-198
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• 2013

In the present study we evaluated drug-drug interaction potential of ambroxol and cetirizine mediated by inhibition of CYP isoforms including CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4 using pooled human liver microsomes (HLMs). As measured by liquid chromatography-electrospray ionization tandem mass spectrometry, cetirizine and ambroxol inhibited significantly CYP2E1 but the maximal inhibition was approximately 36% at 10 ${\mu}M$ cetirizine and 28% at 3 ${\mu}M$ ambroxol. In addition, CYP2D6 activity was decreased to approximately 83% of control activity in pooled HLM incubated with 3 ${\mu}M$ ambroxol. Activities of CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, and CYP3A4 were not significantly inhibited by cetirizine and ambroxol. Considering their maximal plasma concentration in human ($C_{max}$ of cetirizine is approximately 0.67 ${\mu}M$ and $C_{max}$ of ambroxol is 0.044 ${\mu}M$), these two drugs have very low possibility in drug-drug interaction by CYP inhibition in clinical situations.

• Archives of Pharmacal Research
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• v.29 no.2
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• pp.172-177
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• 2006

Hepatotoxic potential of 2, 3-dibromopropene (2, 3-DBPE) and its conjugation with glutathione (GSH) were investigated in male ICR mice. Treatment of mice with 20, 50, and 100 mg/kg of 2, 3-DBPE for 24 h caused elevation of serum alanine aminotransferase and aspartate aminotransferase activities. The hepatic content of GSH was not changed by 2, 3-DBPE. Meanwhile, the GSH content was slightly reduced when mice were treated with 2, 3-DBPE for 6 h and significantly increased 12 h after the treatment. Subsequently, a possible formation of GSH conjugate of 2, 3-DBPE was investigated in vivo. After the animals were treated orally with 20, 50, and 100 mg/kg of 2, 3-DBPE, the animals were subjected to necropsy 6, 12, and 24 h later. A conjugate of S-2-bromopropenyl GSH was identified in liver and serum treated with 100 mg/kg of 2, 3-DBPE by using liquid chromatography-electrospray ionization tandem mass spectrometry. The protonated molecular ions $[M+H]^+$ of S-2-bromopropenyl GSH were observed at m/z 425.9 and 428.1 in the positive ESI spectrum with a retention time of 6.35 and 6.39 min, respectively. In a time-course study in livers following an oral treatment of mice with 100 mg/kg of 2, 3-DBPE for 6, 12, and 24 h, the 2, 3-DBPE GSH conjugate was detected maximally 6 h after the treatment. The present results suggested that 2, 3-DBPE-induced hepatotoxicity might be related with the production of its GSH conjugate.

• Journal of the Korean Chemical Society
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• v.55 no.4
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• pp.626-632
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• 2011

Phoxim, which is one of veterinary drugs, is a well-known antiparasitic agent in wide use. In this paper, phoxim was extracted from cattle and pig tissue using solid-phase extraction (SPE) employing a silica cartridge with acetonitrile. Liquid chromatography/electrospray ionization-tandem mass spectrometry (LC/ESI-MS/MS) for the analysis of phoxim from animal tissue was presented. Phoxim was detected on a $C_{18}$ column ($2.1{\times}100\;mm$, $3.5\;{\mu}m$) using a mobile phase of 0.1% formic acid in water and acetonitrile. A linear correlation observed in the calibration curves for cattle (0.0048~2.0 mg/kg) and pig (0.0055~2.0 mg/kg) showed above $r^2$=0.995. Accuracy measured at concentrations ranging from 0.0048 to 0.2 mg/kg was the range of 68.2~106.9%. Limit of detection (LOD) and limit of quantitation (LOQ) were the range of 0.0014~0.0017 mg/kg and 0.0048~0.0055 mg/kg, respectively. The precision (RSD%) was below 11.2%.

• Journal of Pharmaceutical Investigation
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• v.34 no.6
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• pp.513-519
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• 2004

A sensitive method for quantification of pinaverium bromide in human plasma was established using liquid chromatography-electrospray ionization tandem mass spectrometry(LC-ESI-MS/MS). Glimepiride was used as internal standard. Pinaverium bromide and internal standard in plasma sample were extracted using tert-butylmethylether(TBME). A centrifuged upper layer was then evaporated and reconstituted with mobile phase of acetonitrile-5 mM ammonium formate (80/20, pH 3.0). The reconstituted samples were injected into a $C_{18}$ reversed-phase column. Using MS/MS with multiple reaction monitoring (MRM) mode, pinaverium and glimepirde were detected without severe interference from human plasma matrix. Pinaverium produced a protonated precursor ion $([M+H]^+)$ at m/z 510.3 and a corresponding product ion at m/z 228.9. Internal standard produced a protonated precursor ion $([M+H]^+)$ at m/z 491.5 and a corresponding product ion at m/z 352.0. Detection of pinaverium bromide in human plasma was accurate and precise, with limit of quantitation at 0.5 ng/ml. The method has been successfully applied to bioavailability study of pinaverium bromide tablet in Korean healthy male volunteers. Pharmacokinetic parameters such as $AUC_t,\;C_{max},\;T_{max},\;K_{el}\;and\;t_{1/2}$ were calculated.

• Analytical Science and Technology
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• v.29 no.4
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• pp.155-161
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• 2016

Distribution of various illegal or counterfeit drugs of seven approved erectile dysfunction drugs and their analogues has been increased, causing health problems such as cardiovascular disorder, tachycardia, headache, or vision disturbance. We used liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) to determine the erectile dysfunction drugs and their analogues in various counterfeit drugs. Eleven erectile dysfunction drugs and their analogues were detected, with sildenafil and its analogues being the most counterfeited compounds (73.8 %), followed by tadalafil and its analogues (25.4 %). The limits of detection (LOD) and the limits of quantitation (LOQ) of liquid-type and solid-type negative samples ranged from 0.1 to 3.3 ng/mL or ng/g and from 0.3 to 10.0 ng/mL or ng/g, respectively. The recoveries ranged from 84.3 to 112.3 % and 83.2 to 110.2 %, respectively. The contents of sildenafil and tadalafil in the various counterfeit drugs ranged from 21.0 to 947.5 mg/g and from 0.2 to 170.2 mg/g, respectively.

• Toxicological Research
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• v.26 no.2
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• pp.101-108
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• 2010

Halogenated organic compounds, such as 1-bromobutane (1-BB), have been used as cleaning agents, agents for chemical syntheses or extraction solvents in workplace. In the present study, immunotoxic effects of 1-BB and its conjugation with glutathione (GSH) were investigated in female BALB/c mice. Animals were treated orally with 1-BB at 375, 750 and 1500 mg/kg in corn oil once for dose response or treated orally with 1-BB at 1500 mg/kg for 6, 12, 24 and 48 hr for time course. S-Butyl GSH was identified in spleen by liquid chromatography-electrospray ionization tandem mass spectrometry. Splenic GSH levels were significantly reduced by single treatment with 1-BB. S-Butyl GSH conjugates were detected in spleen from 6 hr after treatment. Oral 1-BB significantly suppressed the antibody response to a T-dependent antigen and the production of splenic intracellular interlukin-2 in response to Con A. Our present results suggest that 1-BB could cause immunotoxicity as well as reduction of splenic GSH content, due to the formation of GSH conjugates in mice. The present results would be useful to understand molecular toxic mechanism of low molecular weight haloalkanes and to develop biological markers for exposure to haloalkanes.