• 분석과학
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• 제18권4호
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• pp.271-277
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• 2005

혈액 내 urea는 임상진단 시 신장 기능을 판단하는 중요한 표지물질로서 측정되고 있다. 단백질 등 질소화합물의 최종 대사물인 urea는 콩팥의 사구체에서 걸러져 소변으로 배출되는데, 사구체의 거르는 능력이 저하되면 결국 혈액 속의 urea 농도가 증가하게 되어 신장 기능의 정상여부를 판단할 수 있게 된다. 이러한 임상진단 결과의 신뢰성 향상을 위해서는 측정결과가 일차분석법으로 인증된 인증표준 물질과 소급성 고리를 유지해야 한다. 본 연구에서는 혈청 내 urea의 일차분석법으로서 $15^N_2$-urea를 내부 표준물질로 사용하는 동위원소희석 액체크로마토그라피-질량분석법 (ID-HPLC/MS)을 개발하였다. 이 방법은 측정원리상 고도의 정확성이 확보될 뿐 아니라 별도의 유도체화가 필요 없기 때문에 빠르고 편리하다. $C_{18}$-분리관에 0.1 mmol/L $NH_4Cl$ buffer를 이동상으로 사용하여 urea를 분리하였는데, 이 완충용액은 비교적 분자량이 작은 urea를 질량분석하는데 방해가 크지 않은 장점이 있다. HPLC와 질량분석기의 인터페이스로서 positive mode의 electrospray ionization (ESI)를 사용하여 높은 감도와 재현성을 성취하였다. 국제적으로 인정된 인증표준물질의 분석을 통해 최적화된 방법의 유효성을 확인하였으며, 국제비교시험에도 참여하여 좋은 결과를 얻었다. ISO guide에 따라 불확도를 계산하였으며, 확장 불확도는 95% 신뢰도에서 약 1.8%로 나타났다. 이 분석법은 표준연에서 개발 중인 혈청인증표준물질을 인증하는 일차기준측정절차로도 사용되고 있다.

• 대한수의학회지
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• 제44권1호
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• pp.23-28
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• 2004

We established a new method to analyze moxidectin using high performance liquid chromatography(HPLC) with fluorescence derivatization in order to obtain its residual profiles in biological samples. Recovery of moxidectin in tissue was 62% at 10 ppb. Average detection reproducibility in terms of coefficience variation was 4.47% at 0.32 to 10 ppb. Residual of moxidectin was studied in 44 Yorkshire-Landrace mixed bred male pigs administered subcutaneously 0, 200, or $800{\mu}g/kg$ body weight (BW) Residual profiles of moxdectin in blood, muscle, liver, kidney and fat of pigs were described. The concentration of the moxidectin in liver after administration of moxidectin was the highest among the tissues examined. Moxidectin in liver after administration of moxidectin as $200{\mu}g/kg$ BW was declined from $10.0{\pm}3.7ng/g$ at 10 day post administration to $0.5{\pm}0.3ng/g$ level at 40 day post administration. Residual levels of moxidectin in all samples were estimated to fall below the limit of quantitation (0.32 ng/ml) after 50 day after treatment of $200{\mu}g/kg$. Moxidectin showed no abnormal observations in all the clinical findings at any concentrations under these experimental conditions. In conclusion, this analysis method by HPLC after fluorescence derivatization was very effective for the detection of moxidectin in biological samples. We suggest that 50-day is safe enough for the withdrawal time of moxidectin in pigs, following the recommendation dose by the manufacturer.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.242.1-242.1
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• 2003

The bioequivalence of two tablet formulations of 12.72 mg domperidone maleate (Shinpoong "$\textrm{Dompi}^{?}$" tablets vs. Janssen Korea "$\textrm{Dompi}^{?}$" tablets) was assessed in healthy Korean volunteers after oral administration in a randomized crossover study. Blood samples were collected at specified time intervals, and plasma concentration was measured as the amount of domperidone base using a validated HPLC method. The pharmacokinetic parameters of $AUC_{0{\longrightarrow}48}$, $C_{max}$, $T_{max}$$t\frac{1}{2}$ were determined from plasma concentration-time profile of two formulations. (omitted)

• 한국산업보건학회지
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• 제6권1호
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• pp.77-87
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• 1996

다량의 연을 사용하는 제조업 중에서 7개의 축전지 제조업, 3개의 폐전지 제련공장, 그리고 2개의 연분 및 광명단을 제조 또는 사용하는 사업장 총 11개 대상 사업장에서 정기 보건관리시 혈중 Zinc Protoporphyrin 농도를 고려하여 생산직 남자 근로자 234명을 선정, 혈액에서 혈중연, 혈중 ZPP, 혈색소 등을 측정하고 소변에서 ${\delta}$-ALA 배설량을 비색법과 HPLC법으로 분석하여 그 차이점을 확인하고 연노출 지표들과의 관련성을 조사하여 연중독 판정기준의 새로운 기준을 마련하기 위하여 본 연구를 시도한 바 결과는 다음과 같다. 1. 비색법과 HPLC법에 의한 요중 ${\delta}$-ALA 배설량은 높은 상관성이 있으나 비색법이 HPLC법 보다 2 mg/L 정도 높게 측정되었다(r = 0.989, 회귀식 ; HALA = - 0.8194 + 0.8110 ${\times}$ CALA) 2. 요중 ${\delta}$-ALA 배설량은 두 방법 모두 혈중연 및 혈중 ZPP 농도와의 상관계수가 각각 0.46, 0.37 이상이었으며, ${\delta}$-ALA 배설량을 대수변환하였을 때는 상관계수가 0.63, 0.57로 높아졌으며 통계적으로도 유의하였다. 3. 혈중 ZPP를 독립변수로, 비색법과 HPLC법에 의한 요중 ${\delta}$-ALA 배설량을 종속변수로 한 단순회귀방정식은 다음과 같다. CALA = 2.0421 + 0.0341 ${\times}$ ZPP $R^2=0.1385$ p = 0.0001 HALA = 0.8006 + 0.0280 ZPP $R^2=0.1389$ p = 0.001 4. 혈중연을 독립변수로, 비색법과 HPLC법에 의한 요중 ${\delta}$-ALA 배설량을 종속변수로 한 단순 회귀 방정식은 다음과 같다. CALA = - 0.4134 + 0.1545 ${\times}$ PbB $R^2=0.2085$ p = 0.0001 HALA = - 1.2893 + 0.1287 ${\times}$ PbB $R^2=0.2154$ p = 0.0001 5. 비색법과 HPLC법에 의한 요중 ${\delta}$-ALA 배설량을 대수변환하였을 때 혈중연 및 혈중 ZPP를 독립변수로 하는 회귀식은 다음과 같다. logHALA = 0.3078 + 0.0060 ${\times}$ ZPP $R^2=0.3329$ p = 0.0001 logCALA = 1.0189 + 0.0044 ${\times}$ ZPP $R^2=0.3290$ p = 0.0001 logHALA = - 0.0221 + 0.0246 ${\times}$ PbB $R^2=0.4046$ p = 0.0001 logCALA = 0.7662 + 0.0184 ${\times}$ PbB $R^2=0.4108$ p = 0.0001 6. 요중 ${\delta}$-ALA 배설량에 대한 연중독 주의한계의 cut-off point를 5 mg/L로 하였을 경우 혈중연과 혈중 ZPP의 주의한계에 대한 비색법의 누적 빈도가 HPLC법 보다 높았으며, 따라서 HPLC법의 cut-off point를 3 mg/L로 하였을 때 비색법과 좋은 일치도를 보였고 연노출지표들과 량-반응 관계를 나타내었다. 이상의 결과로 연중독 판정기준의 주의한계와 선별한계의 개정이 필요하나 남자 근로자들만의 연구이므로 여자 근로자에 관한 연구가 추가로 필요하다고 생각된다.

• 분석과학
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• 제27권2호
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• pp.92-99
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• 2014

본 연구에서는 음이온 고체상 추출법 (AE SPE; anion exchange solid phase extraction)을 사용하여 간섭요인을 제거한 후, 친화 크로마토그래피 AF HPLC; affinity high performance liquid chromatography)와 유도결합 플라스마 질량분석법 (ICP/MS; inductively coupled plasma/mass spectrometry)을 사용하여 한국인의 혈청에서의 셀레노 단백질을 분리하고 정량하였다. 먼저 동위원소 희석법으로 셀레늄 총량을 분석한 결과, 건강한 한국 사람의 혈청내 평균농도는 $94.3{\pm}2.3ngg^{-1}$ 이었다. AE SPE와 AF 컬럼을 online으로 연결하여 셀레노단백질인 glutathione peroxidase (GPx), selenoprotein P (SelP), selenoalbumin (SeAlb)을 분리하고, 후 컬럼 동위원소 희석법 (PC ID; post column isotope dilution)으로 정량하였다. 혈청 인증표준물인 BCR-637을 분석한 결과 전체 셀레노 단백질의 합은 $85.4{\pm}3.4ngg^{-1}$으로 문헌값인 $81{\pm}7ngg^{-1}$과 일치하는 결과를 얻을 수 있었다. 20 명의 건강한 한국인의 혈청에서 얻은 셀레노 단백질 GPx, SelP 및 SeAlb 의 농도는 각각 $12.1{\pm}1.4ngg^{-1}$, $57.2{\pm}2.0ngg^{-1}$, 그리고 $20.0{\pm}1.9ngg^{-1}$ 이었으며 이들의 합인 $89.3ngg^{-1}$은 셀레늄의 총량값인 $94.3ngg^{-1}$과 거의 같은 값으로 혈청에서의 셀레늄은 주로 셀레노 단백질로 구성되어 있음을 알았다. 이 중 GPx의 농도는 간섭을 제거하기 전인 $25.0ngg^{-1}$에 비해 50% 이상 크게 감소하였는데 이로서 간섭은 주로 GPx에 포함되어 있음을 확인할 수 있었다. AE SPE는 간섭요인인 Cl과 Br을 제거 하는데 매우 효과적임을 보여주었다.

• Biomolecules & Therapeutics
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• 제3권1호
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• pp.91-96
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• 1995

The effects of toluene inhalation on the contents of amino acid neurotransmitters in rat brain were investigated and blood toluene concentrations inducing changes of behavior and amino acid neurotransmitter contents in rat brain were observed. Male wistar rats were exposed to toluene vapor (single dose : 1700, 5000 and 10000 ppm for 2 hrs, repeated dose : 1700 and 5000 ppm for 2 hrs/day$\times$6 days). Toluene concentrations in blood and the inhalation chamber were assayed by GC with headspace sampler. HPLC method following PITC derivatization was used to measure the amino acid contents in brain tissues such as frontal cortex, caudate, hippocampus, cerebellum and brain stem. Glutamic acid and aspartic acid levels were increased by single inhalation of toluene (5000 ppm) in all the brain areas assayed in this experiment. In caudate and cerebellum, taurine levels were decreased by single inhalation of low dose toluene (1700 ppm), but increased by repeated administration. At high blood toluene concentration, GABA levels were increased in all the brain areas assayed in this experiment and the increasing extents of inhibitory amino acid contents measured in caudate and hippocampus were greater than those of excitatory amino acids. These results suggest that the changes of amino acid neurotransmitter contents in brain by exposure to toluene may modulate toluene-induced behaviors.

• 한국동물위생학회지
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• 제36권4호
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• pp.311-320
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• 2013

The purpose of this study was to evaluate detecting methods and the relationship between tissues and blood for enrofloxacin and metabolic ciprofloxacin residues in broiler chickens. Two groups of broiler chickens were administrated via the drinking water with $50{\mu}g/mL$ and $100{\mu}g/mL$ of enrofloxacin for 5 days, respectively. The concentration of enrofloxacin and metabolic ciprofloxacin in tissues (muscle and kidney) and blood were measured during administration period (for 5 days) and withdrawal period (for 12 days) by high performance liquid chromatography (HPLC) method. Also, all samples were conducted for screening of residues by microbial method using E. coli for quinolone detection and immuno-chromatography method using Smart kit. The relationship between tissues (muscle and kidney) and blood for enrofloxacin and metabolic ciprofloxacin residues in broiler chickens was followed : The levels of enrofloxacin and metabolic ciprofloxacin residues in muscle and kidney were higher 2.9~3.2 folds, 3.6~3.8 folds more than the residues levels in blood, respectively. These results support we can predict the residues in muscle and kidney from the residues in blood. In comparison of detecting methods for antibiotic residues, microbial method using E. coli for quinolone detection and immuno-chromatography method using Smart kit could detect positive reaction at similar or lower concentration than violative concentration of enrofloxacin and metabolic ciprofloxacin in chicken tissues. These results support what two screening methods are useful for screening of quinolone detection in chickens.

• 한국임상약학회지
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• 제10권1호
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• pp.25-29
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• 2000

Bioequivalence of cisapride-containing $Cisaplus^{(R)}$ tablets (Daewoong Co.) to reference $Prepulsid^{(R)}$ tablets (Janssen Co.) was evaluated according to the guidelines of Korea Food and Drug Administration (KFDA). Sixteen healthy volunteers were divided randomly into two groups and administered orally at a cisapride dose of 10 mg in a $2\times2$ crossover design. There was a 1-week washout period between the treatments. Blood samples were taken at predetermined time intervals for 48 hr and the plasma cisapride concentrations were determined by an HPLC with UV detector. The area under the plasma drug concentration-time curve (AUC) was caltulated from time zero to the last sampling time by a linear trapezoidal method. The maximum observed plasma drug concentration ($C_{max}$) and the time to $C_{max}\;(T_{max})$ were estimated directly from the drug concentration-time data. Analysis of variance (ANOVA) showed that the apparent differences for AUC, $C_{max}\;and\;T_{max}$ were $-7.52\%,\;-8.91\%\;and\;-15.55\%$, respectively. The minimum detectable differences for AUC, $C_{max}\;and\;T_{max}$ between formulations were $14.52\%,\;11.57\%\;and\;28.00\%$ respectively, at $\alpha=0.05\;and\;1-\beta=0.8\;levels.\;The\;90\%$ confidence intervals for AUC, $C_{max}\;and\;T_{max}\;were\;-16.00\sim0.97\%,\;-15.67\sim-2.15\%\;and\;-31.88\%\sim0.84\%$, respectively. These results satisfy the bioequivalence criteria of KFDA guidelines, indicating that the two formulations of cisapride are bioequivalent.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제25권4호
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• pp.304-310
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• 1999

This study was designed to find the effect of Minocycline loaded microcapsule applied locally to tissue by measuring drug concentration in tissue and serum by HPLC and to achieve optimal drug delivery system and duration to a specific target site. Control group were administrated minocycline intramuscularly twice a day with $0.2{\mu}g/100g$ for 1 to 10 days. In experimental group, surgical wound was created on Rt. cheek and then minocycline loaded microcapsule was applied into the space between superficial and deep layer of masseter muscle. Animals were sacrificed at 1, 3, 5, 7, 10 days after initial administration, blood was obtained from heart and right masseter muscle was excised. Blood sample was centrifuged at 3000rpm for 15min. Tissue sample was homogenized, left at room temperature for 48hr and centrifuged at 4000g for 5min. Supernatant was completely dried and dissolved in distilled water. Analysis was conducted using a ${\mu}Bondapack$ C18 column. The mobile phase was 0.2M Ammonium Oxalate/0.1M EDTA/DMF=11/4/5 solution, which was injected into the column and detected with photodiode detector at 344nm wavelength. The results were as follows : 1. This method was reliable, could be replicated and suitable for minocycline analysis in tissue as well as serum. 2. In tissue, concentration of minocycline of experimental group was higher than that of control group for 5days. 3. Except 1 day, concentration of minocycline in serum of experimental group was lower than that of control group. 4. Concentration of minocycline in tissue was much higher than that in serum. From these results, minocycline loaded microcapsule might be effective tool for local drug delivery system might be useful for treatment of infections of oral and maxillofacial region and management of infected surgical wound, minimizing systemic effects.

• Journal of Pharmaceutical Investigation
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• 제23권3호
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• pp.165-177
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• 1993

The relationship between the plasma haloperidol (HP) concentration and clinical response, and the effects of its active metabolite, reduced haloperidol (RH) on clinical response of HP were investigated in schizophrenic patients. In clinical study I, with 17 schizophrenic patients (male 8, fermale 9) who were administered with three different fixed doses of HP (15, 30 and 50 mg/day) for 3 weeks, the concentrations of HP and RH in plasma and blood and clinical response had been checked before and every week during the study. The clinical response was evaluated by the method of brief psychiatric rating scale (BPRS), and relative improvement of clinical response based on baseline BPRS (before drug treatment) was calculated. The concentrations of HP and RH in plasma and blood were assayed by HPLC. In clinical study II, the plasma RH/HP concentration ratios were checked in 11 patients who were administered with high doses of HP, over 60 mg a day, because of the poor clinical response at usual doses of HP. Plasma HP concentration and relative improvement of BPRS at 3 week in schizophrenic patients showed a 'curvilinear' relationship, and the clinical response was improved relatively over 50% based on the baseline BPRS in the range of $5{\sim}57\;ng/ml $ of HP in plasma. Also, the plasma RH concentrations were increased nonlinearly as the plasma HP concentration increased, and in high plasma HP concentration, over 30 ng/mI, clinical response gradually decreased, while the plasma RH/HP concentration ratio increased nonlinearly. Blood partition coefficients of HP and RH were not changed according to daily HP dose and duration of drug therapy. From these results, it is noted that the higher plasma RH/HP concentration ratio, resulted from the accumulation of RH as HP concentration increased, might explain the 'curvilinear' decrease of HP clinical response.