• YAKHAK HOEJI
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• v.52 no.2
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• pp.137-146
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• 2008

Even though driving under the influence of drug (DUID) is a worldwide problem, we, Korea has no regulation system yet except for alcohol, and there are little cases reported related to DUID. In order to investigate the type of abused drugs for drivers in Korea, we tried to analyze controlled and non-controlled drugs in alcohol-positive blood samples. 275 whole bloods, which were positive for alcohol on the roadside test, were collected from the police for two months ($Nov.{\sim}Dec.$ 2006). The analytical strategy was constituted of three steps: First, alcohol in blood samples were confirmed and quantified by gas chromatography. Second, controlled drugs were screened by $Evidence_{investigator}\;^{TM}$ (Randox, U.K.) as preliminary test. It was based on immunoassay by biochip array analyzer. Nine groups of drug abuse were screened: amphetamines, methamphetamines, cannabis, cocaine, opiates, barbiturates, methadone, benzodiazepines I (oxazepam) & II (lorazepam). Finally, confirmation of these drugs was performed by GC-MS. Blood samples were extracted by solid-phase extraction by $RapidTrace^{TM}$ (Zymark, U.S.A.). After trimethylsilyl (TMS) derivatization, eluates were analyzed to GC-MS. Total 49 drugs were investigated in this study including controlled drugs, antidepressants, 1st generation antihistamines, dextromethorphan, nalbuphine, ketamine, etc. For rapid detection, we developed the automated identification system. It was made up a new software, "DrugMan", modified Chemstation data analysis menu and newly developed macro modules. A series of peak selection, identification and reporting of the results were performed automatically by this system. Concentrations of alcohol in 275 blood samples were ranged from 0.011 to 0.249% (average, 0.119%). Among 149 blood samples, just six samples (4.0%) were showed positive results to the immunoassay: one methamphetamine and five benzodiazepines group I. By GC-MS confirmation, only benzodiazepines were detected and methamphetamine was not detected from immunoassay positive blood sample. Besides these drugs, 5 chlorpheniramines, dextromethorphan, diazepam, doxylamine, ibuprofen, lidocaine and topiramate were also detected in whole bloods by GC-MS. Conclusively, the frequency of drug abuse for Korean drivers was relatively low. There was none case which illegal drug was detected. However these results were limited to alcohol positive blood samples, so it is necessary to analyze more samples including alcohol negative blood.

• Near Infrared Analysis
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• v.1 no.2
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• pp.29-33
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• 2000

The identification step of raw drug materials is an indispensible procedure in the GMP manufacturing process within the pharmaceutical industry. However, wet chemistry methods for identification of drug materials, used by the various Pharmacopeia are time-consuming and expensive steps. In this paper, near-infrared spectroscopy (NIRS) has been developed for identifying eleven drug substances including calcium pantothenate, cefaclor, cefoperazone, cephradine, dextromethorphan, ehtambutol, nicotinamide, pyrozinamide, tramadol, vitamin C, and vitamin E. Also the aim of ths work is to consturct a new algorithm for calibration model using soft independence modeling of class analogy (SIMCA) with Malinowskis Indicator Function (IND), which is used for finding the number of principal components of each class of the SIMACA model. The use of NIR technique with pattern recognition to qualify raw materials can make it possible to monitor process in real time as well as to control all procedures in the pharmaceutical industry. As the result, the samples identified of 183 different batches from 11 different compounds were separated clearly by SIMCA with 2nd derivative spectra in the NIR region of 1100∼2400 nm.

• Journal of The Korean Society of Clinical Toxicology
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• v.1 no.1
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• pp.34-39
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• 2003

Carisoprodol (CSP) is commonly prescribed as a skeletal muscle relaxant. Recently, we encountered 7 suicidal cases in which carisoprodol was detected. We developed a rugged, sensitive, and specific method for the determination of CSP and meprobamate (MPB) by GC and GC/MS. Postmortem blood concentrations of CSP and MPB ranged 22.9-124.4 ,$\mu$g/ml and its metabolite, 26.8-144.5 ,$\mu$g/ml respectively. Among 7 cases studied, Only CSP was ingested in 4 cases and combination of CSP and dextromethorphan was ingested in 2 cases according to the case history and one case was with ethanol. The order of the tissue concentration of CSP and MPB was liver> kidney > brain, and the concentration of MPB was higher than that of CSP in all tissues. The MPB /CSP concentration ratios of urine, bile juice, liver, kidney, brain and blood were 15.7, 4.0, 1.2, 1.4, 1.4 and 1.0 respectively. There was a big difference in concentration of CSP and MPB in 7 cases due to differences in the amount of dose administered and time to death after dosing.

• The Journal of Korean Medicine
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• v.24 no.2
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• pp.40-46
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• 2003

Objectives : Achyranthes bidentata radix (Usul) has been used as anti-arthritic, antiallergic, antidiuretic, and so on. Recently extracts of Achyranthes bidentata radix have shown anti-inflammatory and cancer preventive effects in vitro and in vivo. Methods : We therefore evaluated the inhibitory potential of ethanol extracts of Achyranthes bidentata radix on cytochrome P450 (CYP) isoforms-catalyzed reactions, which relate to causes of cancer and inflammation, including CYP1A2, CYP2C9, CYP2C19, CYP2E1, CYP2D6, CYP2C8, and CYP3A4, using human liver microsomal preparations. Results : The extracts showed weak or negligible inhibitory effects on CYP2C9-catalyzed (S)-warfarin 7-hydroxylation, CYP2C19-catalyzed S-mephenytoin 4-hydroxylation, and CYP2D6-catalyzed dextromethorphan O-demethylation with each IC50 over 1750 g/ml, respectively. However, it showed relatively significant inhibitory effect on CYP1A2-catalyzed phenacetin O-deethylation and CYP2E1-catalyzed chlorzoxazone 6-hydroxylation with IC50s of 970.5 g/ml and 821.4 g/ml, respectively. Conclusions : These results suggest that extracts of Achyranthes bidentata radix have inhibitory effects on CYP-catalyzed reactions, especiallyCYP1A2 and CYP2E1, in human liver microsomes. These effects appear to relate to anti-inflammatory and cancer prevention following decrease of reactive oxygen species formed by CYP, especially CYP1A2 and CYP2E1, by Achyranthes bidentata radix. However, further evaluation is necessary to demonstrate and to confirm its effects in human.

• Korean Journal of Pharmacognosy
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• v.1 no.3
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• pp.93-99
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• 1970

There have been reported by several workers for the isolation and determination of the amine derivatives as Metbylephedrine Hydrochloride and Ephedrine Hydrochloride adopting neutralization method, steam distillation method, non-aqous titration method, ion-exchange resin method, titration method after acetylation, colorimetric method, gravimetric method, iodine titration method and gas chromatography. Those methods mentioned in above, can be practically applied for the sample which is not mixed one mith the other amine compounds. Presently, it has not shown on the isolative determination of the mixed sample of amine derivatives. In this paper, it is discussed on the isolative determination of Methylephedrine Hydrochloride as the tertiary amine compound and Ephedrine Hydrochloride as the secondary amine compound. According to the results of the experiment, it could be summarized as follows: 1. There is no time-variation on the color reaction of Methylephedrine Hydrochloride and Ephedrine Hydrochloride with the color reagent, bromcresolgreen. And Methylephedrine Hydrochloride and Ephedrine Hydrochloride, respectively, can be determined spectrophotometrically by means oft his color reaction. 2. For the isolation of Methylephedrine Hydrochloride and Ephedrine Hydrochloride from the mixed sample, Methylephedrine Hydrochloride can be eluted by chloroform, while Ephedrine Hydrochloride by the mixed solvent of chloroform and ethylalcohol (2:1), from the celite column adsorbed at pH6.4 followed by extraction with ether undersodium hydroxide alkali re action. 3. When the sample is mixed with quinine hydrochloride, dihydrocodeine bitartate, and noscapine, these mixed compounds can be eliminated by means of stram distillation. 4. When the sample is mixed with chlorpheniramine maleate, dextromethorphan hydrobromide and diphenhydramine hydrochloride, the mixed compounds can be eliminated by means of steam distillation and celite adsorption column chromatography, In conclusion, the isolative determination method for Methylephedrine Hydrochloride and Ephedrine Hydrochloride studied in this paper, indicates with the excellent reproducibility and accuracy.

• YAKHAK HOEJI
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• v.57 no.2
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• pp.87-94
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• 2013

An analytical methodology based on solid-space extraction (SPE) with with Bond Elut Certify cartridge (Varian, 130 mg) has been developed for the qualification and quantitation of strychnine in blood. After the elution layer was evaporated, the residue was reconstituted with methanol for GC/MS. Internal standard was used 10 mg/l dextromethorphan. Strychnine is a potent central nervous stimulant and convulsant, and an alkaloid found in seeds of Strychnos nux-vomica. It was used therapeutically to improve circulation and muscle tone in oral or intramuscular doses of 0.05~8 mg. The fatal dose of strychnine for humans is 50~100 mg. A man was found dead lying curled up the corner of the large room in a roof house after the fire fighter opened a locked door inside to put out the fire. The postmortem blood and gastric contents were analyzed for toxicological testing. Strychnine and brucine were detected using GC/MS first in gastric contents extracts. The contents of strychnine was 0.083 mg/l in heart blood, 0.088 mg/l in peripheral blood and 4.0 mg/kg in gastric contents, respectively. Method validation was carried out in terms of linearity, accuracy, precision (intraday, interday) in blood. The assay is linear over 0.05~10 mg/l ($r^2$=0.999). Limit of detection (LOD) and limit of quantitation (LOQ) in blood were determined 0.02 mg/l (S/N=3) and 0.07 mg/l (S/N=10), respectively. Accuracy (bias%) of strychnine with 0.1, 1 and 10 mg/l was 12.0% (n=6), 9.3% (n=6) and 6.9% (n=6), respectively. Intraday precision (CV%) of strychnine with, 0.1, 1 and 10 mg/l were 6.4%, 10.4%, 1.2% (n=6), respectively. Interday precision (CV%) of strychnine with 0.1, 1 and 10 mg/l over three days were 24.0%, 18.5%, 13.8% (n=18), respectively. Relative recovery with 0.1, 1 and 10 mg/l (in blood) were 114.9%, 99.3% and 87.4% (n=6), respectively. The described method can be applied in forensic toxicology to determine strychnine in blood samples.

• Journal of Microbiology and Biotechnology
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• v.22 no.12
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• pp.1659-1664
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• 2012

TSAHC [4'-(p-toluenesulfonylamido)-4-hydroxychalcone] is a promising antitumorigenic chalcone compound, especially against TM4SF5 (four-transmembrane L6 family member 5)-mediated hepatocarcinoma. We evaluated the potential of TSAHC to inhibit the catalytic activities of nine cytochrome P450 isoforms and of P-glycoprotein (P-gp). The abilities of TSAHC to inhibit phenacetin O-deethylation (CYP1A2), coumarin 6-hydroxylation (CYP2A6), bupropion hydroxylation (CYP2B6), amodiaquine N-deethylation (CYP2C8), diclofenac 4-hydroxylation (CYP2C9), omeprazole 5-hydroxylation (CYP2C19), dextromethorphan O-demethylation (CYP2D6), chlorzoxazone 6-hydroxylation (CYP2E1), and midazolam 1'-hydroxylation (CYP3A) were tested using human liver microsomes. The P-gp inhibitory effect of TSAHC was assessed by [$^3H$]digoxin accumulation in the LLCPK1-MDR1 cell system. TSAHC strongly inhibited CYP2C8, CYP2C9, and CYP2C19 isoform activities with $K_i$ values of 0.81, 0.076, and $3.45{\mu}M$, respectively. It also enhanced digoxin accumulation in a dose-dependent manner in the LLCPK1-MDR1 cells. These findings indicate that TSAHC has the potential to inhibit CYP2C isoforms and P-gp activities in vitro. TSAHC might be used as a nonspecific inhibitor of CYP2C isoforms based on its negligible inhibitory effect on other P450 isoforms such as CYP1A2, CYP2A6, CYP2B6, CYP2D6, CYP2E1, and CYP3A.

• Journal of Life Science
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• v.17 no.3 s.83
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• pp.334-339
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• 2007

We evaluated the potential of 20 herbal medications (HMs), commonly used in Korea, to inhibit the catalytic activities of several cytochrome P450 (CYP) isoforms. The abilities of 500 ${\mu}g/ml$ of aqueous extracts of 20 HMs to inhibit phenacetin O-deethylation (CYP1A2), coumarin 6-hydroxylation (CYP2A6), bupropion hydroxylation (CYP2B6), rosiglitazone hydroxylation (CYP2C8), tolbutamide 4-methylhydroxylation (CYP2C9), S-mephenytoin 4'-hydroxylation (CYP2C19), dextromethorphan O-demethylation (CYP2D6), chlorzoxazone 6-hydroxylation (CYP2E1), and midazolam 1'-hydroxylation (CYP3A) were tested using human liver microsomes. The HMs Woohwangcheongsimwon suspension and Hwanglyeonhaedok-Tang strongly inhibited CYP2B6 and CYP2D6 isoform activity, respectively. These results suggest that some of the HMs used in Korea have potential to inhibit CYP isoforms in vitro. Although the plasma concentrations of the active constituents of the HMs were not determined, some herbs could cause clinically significant interactions because the usual doses of those individual herbs are several grams of freeze-dried extracts.

• The Korean Journal of Pharmacology
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• v.27 no.2
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• pp.211-214
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• 1991

SJ-200 is an oral liquid preparation of acetaminophen, ibuprofen, Dl-methyleph edrine HCl, caffeine, chlorpheniramine maleate, guaifenesin and dextromethorphan HBr, which is indicated when there is a need to improve various cold symptoms such as headache, sore throat, fever, or cough etc. Thirty patients was enroled for this study fro June to July, 1991. They were given one bottle (30 ml) of SJ-200 t.i.d dy P.O for an average of one to seven days. 1) Twenty-eight patients (84.8%) were relieved from the symptoms of upper respiratory tract infection. 2) Side effects with this preparation occured in 8 patients924.2%) but in four patients, they were mild, which wee transienty by the discontinuation f the medication.