• Journal of Pharmaceutical Investigation
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• 제35권6호
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• pp.423-429
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• 2005

A selective and sensitive reversed-phase HPLC method for the determination of fenoprofen in human serum was developed, validated, and applied to the pharmacokinetic study of fenoprofen calcium. Fenoprofen and internal standard, ketoprofen, were extracted from human serum by liquid-liquid extraction with diethyl ether and analyzed on a Luna C18(2) column with the mobile phase of acetonitrile-3 mM potassium dihydrogen phosphate (32:68, v/v, adjusted to pH 6.6 with phosphoric acid). Detection wavelength of 272 nm and flow rate of 0.25 mL/min were fixed for the study. The assay robustness for the changes of mobile phase pH, organic solvent content, and flow rate was confirmed by $3^{3}$ factorial design using a fixed fenoprofen concentration $(2\;{\mu}g/mL)$ with respect to its peak area and retention time. And also, the ruggedness of this method was investigated at three different laboratories using same quality control (QC) samples. This method showed linear response over the concentration range of $0.05-100\;{\mu}g/mL$ with correlation coefficients greater than 0.999. The lower limit of quantification using 1 mL of serum was $0.05\;{\mu}g/mL$, which was sensitive enough for pharmacokinetic studies. The overall accuracy of the quality control samples ranged from 92.27 to 109.20% for fenoprofen with overall precision (% C.V.) being 5.51-11.71 %. The relative mean recovery of fenoprofen for human serum was 81.7%. Stability (freeze-thaw, short and long-term) studies showed that fenoprofen was not stable during storage. But, extracted serum sample and stock solution were allowed to stand at ambient temperature for 12 hr prior to injection without affecting the quantification. The peak area and retention time of fenoprofen were not significantly affected by the changes of mobile phase pH, organic solvent content, and flow rate under the conditions studied. This method showed good ruggedness (within 15% C.V.) and was successfully used for the analysis of fenoprofen in human serum samples for the pharmacokinetic studies of orally administered Fenopron tablet (600 mg as fenoprofen) at three different laboratories, demonstrating the suitability of the method.

• Journal of Pharmaceutical Investigation
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• 제36권2호
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• pp.89-95
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• 2006

A selective and sensitive reversed-phase HPLC method for the determination of pentoxifylline in human serum was developed, validated, and applied to the pharmacokinetic study of pentoxifylline. Pentoxifylline and internal standard, chloramphenicol, were extracted from the serum by liquid-liquid extraction with dichloromethane and analyzed on a Luna CI8(2) column with the mobile phase of acetonitrile-0.034 M phosphoric acid (25:75, v/v, adjusted to pH 4.0 with 10 M NaOH). Detection wavelength of 273 nm and flow rate of 0.8 mL/min were used. This method showed linear response over the concentration range of 10-500 ng/mL with correlation coefficients greater than 0.999. The lower limit of quantification using 0.5 mL of the serum was 10 ng/mL, which was sensitive enough for pharmacokinetic studies of pentoxifylline. The overall accuracy of the quality control samples ranged from 89.3 to 92.7% for pentoxifylline with overall precision (% C.V.) being 4.1-9.2%. The relative mean recovery of pentoxifylline for human serum was 105.8%. Stability (stock solution, short and long-term) studies showed that pentoxifylline was not stable during storage. But three freeze-thaw cycles and extracted serum samples were stable. This method showed good ruggedness (within 15% C.V.) and was successfully applied for the analysis of pentoxifylline in human serum samples for the pharmacokinetic studies of orally administered $Trental^{\circledR}$ tablet (400 mg pentoxifylline), demonstrating the suitability of the method.

• Journal of Pharmaceutical Investigation
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• 제36권1호
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• pp.45-51
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• 2006

A rapid, selective and sensitive reversed-phase HPLC method for the determination of dipyridamole in human serum was developed, validated, and applied to the pharmacokinetic study of dipyridamole. Dipyridamole and internal standard, loxapine, were extracted from human serum by liquid-liquid extraction with diethyl ether and analyzed on a Nova Pak $C_{I8}$ column with the mobile phase of 40 mM ammonium acetate:methanol:acetonitrile (35:35:30)(v/v/v, pH 7.8). Detection wavelength of 280 nm and flow rate of 1.0 mL/min were fixed for the study. The assay robustness for the changes of mobile phase pH, organic solvent content, and flow rate was confirmed by $3^3$ factorial design using a fixed dipyridamole concentration (50 ng/mL) with respect to its peak area and retention time. And also, the ruggedness of this method was investigated at three different laboratories using same quality control (QC) samples. This method showed linear response over the concentration range of 2-2000 ng/mL with correlation coefficients greater than 0.999. The lower limit of quantification using 0.5 mL of serum was 2 ng/mL, which was sensitive enough for pharmacokinetic studies of dipyridamole. The overall accuracy of the quality control samples ranged from 103.94 to 105.86% for dipyridamole with overall precision (% C.V.) being 4.60-11.49%. The relative mean recovery of dipyridamole for human serum was 97.64%. Stability studies showed that dipyridamole was stable during storage, or during the assay procedure in human serum. The peak area and retention time of dipyridamole were not significantly affected by the changes of mobile phase pH, organic solvent content, and flow rate under the conditions studied. This method showed good ruggedness (within 15% C.V.) and was successfully used for the analysis of dipyridamole in human serum samples for the pharmacokinetic studies of orally administered Dimor tablet (75 mg as dipyridamole) at three different laboratories, demonstrating the suitability of the method.

• Journal of Pharmaceutical Investigation
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• 제36권1호
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• pp.23-29
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• 2006

A rapid, selective and sensitive reversed-phase HPLC method for the determination of promethazine in human serum was developed, validated, and applied to the pharmacokinetic study of promethazine. Promethazine and internal standard, chlorpromazine, were extracted from human serum by liquid-liquid extraction with n-hexane containing 0.8% isopropanol and analyzed on a Capcell Pak CN column with the mobile phase of acetonitrile-0.2 M potassium dihydrogen phosphate (42:58, v/v, adjusted to pH 6.0 with 1 M NaOH). Detection wavelength of 251 nm and flow rate of 0.9 mL/min were fixed for the study. The assay robustness for the changes of mobile phase pH, organic solvent content, and flow rate was confirmed by $3^{3}$ factorial design using a fixed promethazine concentration (10 ng/mL) with respect to its peak area and retention time. In addition, the ruggedness of this method was investigated at three different laboratories using same quality control (QC) samples. This method showed linear response over the concentration range of 1-40 ng/mL with correlation coefficients greater than 0.999. The lower limit of quantification using 1 mL of serum was 1 ng/mL, which was sensitive enough for pharmacokinetic studies. The overall accuracy of the quality control samples ranged from 96.15 to 105.40% for promethazine with overall precision (% C.V.) being 6.70-11.22%. The relative mean recovery of promethazine for human serum was 63.54%. Stability (freeze-thaw and short-term) studies showed that promethazine was stable during storage, or during the assay procedure in human serum. However, the storage at $-80^{\circ}C$ for 4 weeks showed that promethazine was not stable. Extracted serum sample and stock solution were not allowed to stand at ambient temperature for 12 hr prior to injection. The peak area and retention time of promethazine were not significantly affected by the changes of mobile phase pH, organic solvent content, and flow rate under the conditions studied. This method showed good ruggedness (within 15% C.V.) and was successfully used for the analysis of promethazine in human serum samples for the pharmacokinetic studies of orally administered Himazin tablet (25 mg as promethazine hydrochloride) at three different laboratories, demonstrating the suitability of the method.

• Journal of Pharmaceutical Investigation
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• 제36권5호
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• pp.331-338
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• 2006

A rapid, selective and sensitive reverse-phase HPLC methods for the determination of atenolol and chlorthalidone in human serum and whole blood were validated, and applied to the pharmacokinetic study of atenolol and chlorthalidone combination therapy. Atenolol and an internal standard, pindolol, were extracted from human serum by liquid-liquid extraction, and analyzed on a $\mu$-Bondapak C18 $10-{\mu}$ column in a mobile phase of methanol-0.01 M potassium dihydrogenphosphate(30:70, v/v, adjusted to pH 3.5) and fluorescence detection(emission: 300 nm, excitation: 224 nm). Chlorthalidone and an internal standard, probenecid, were extracted form human whole blood by liquid-liquid extraction, and analyzed on a Luna C18 $5-{\mu}$ column in a mobile phase of acetonitrile containing 77% 0.01 M sodium acetate and UV detection at 214 nm. These analysis were performed at three different laboratories using the same quality control(QC) samples. The chromatograms showed good resolution, sensitivity, and no interference by human serum and whole blood, respectively. The methods showed linear responses over a concentration range of 10-1,000 ng/mL for atenolol and 0.05-20 ${\mu}g/mL$ for chlorthalidone, with correlation coefficients of greater than 0.999 at all the three laboratories. Intra- and inter-day assay precision and accuracy fulfilled international requirements. Stability studies(freeze-thaw, short-, long-term, extracted sample and stock solution) showed that atenolol and chlorthalidone were stable. The lower limit of quantitation of atenolol and chlorthalidone were 10 ng/mL and 0.05 ${\mu}g/mL$, respectively, which was sensitive enough for pharmacokinetic studies. These methods were applied to the pharmacokinetic study of atenolol and chlorthalidone in human volunteers following a single oral administration of Hyundai $Tenoretic^{\circledR}$ tablet(atenolol 50 mg and chlorthalidone 12.5 mg) at three different laboratories.

• 한국측량학회지
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• 제40권2호
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• pp.119-133
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• 2022

측량, 지도, 통신 기술의 발달로 다양한 길안내 앱 및 차량용 내비게이션 등이 개발 및 보급되었다. 그 결과, 보행 및 운전 전반에 널리 활용되며 많은 도움을 주고 있으나 여전히 사회적 약자의 일상 편의를 향상시키는데 있어서는 한계가 존재한다. 이는 일반 길안내 앱이나 내비게이션이 일반인의 보행이나 차량을 중심으로 서비스되고 있어 시각장애인이 이동 시 혼란을 유발하거나 위험 요소가 되는 정보를 제공하지 못하는데 따른 것이다. 이에 본 연구에서는 시각장애인과 같이 보행(이동)에 제약을 받는 교통약자를 대상으로 한 공간정보 기반 서비스를 구현하기 위한 데이터 구축 방안을 모색하고자 하였다. 이를 위해 공간정보 데이터를 기반으로 시각장애인의 보행과 관련되어 요구되는 항목과 구성요소를 선정하고, 이를 기반으로 상용 앱(app)에 접목할 수 있는 보행용 길안내 네트워크를 구성·분석하였다. 그 결과, 공간정보 기반의 점자블럭(점형/선형), 음향신호기, 버스정류장, 볼라드 등의 추가적인 시각장애인용 컨텐츠 정보가 확보될 경우 교통약자의 독립적인 보행을 위한 길안내 서비스가 가능하다는 결론을 도출했다. 또한, 길안내를 위한 데이터 모델을 정립하고 이를 기반으로 초기 버전의 모바일 앱을 구현했으며, 시각장애인을 대상으로 한 검증을 통해 시각장애인용 컨텐츠 정보 제공이 보행 시 유용함을 확인했다. 보다 안정적인 보행을 지원하기 위해서는 타 기관 또는 여러 부처에서 제공되는 공간정보 자료의 DB (DataBase)화 및 활용이 필요하며, 동시에 ICT (Information and Communications Technologies)기술 접목을 통해 다양한 센서 및 음성기술 등을 연계·활용한 고도화 방안도 모색되어야 할 것으로 판단된다.

• 대한토목학회논문집
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• 제1권1호
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• pp.53-68
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• 1981

지속하중하(持續荷重下)의 점토지반(粘土地盤) 또는 사면(斜面)을 형성(形成)하고 있는 점토(粘土)는 시간의존변형(時間依存變形)을 일으키고 어떤 경우 파괴(破壞)에 이르기도 하는데 그 원인(原因)은 점토(粘土)의 Creep 거동(擧動) 때문이라는 보고(報告)가 대부분(大部分)이다. Creep 거동(擧動)은 많은 요소(要素)에 관련될 뿐 아니라 특(特)히 함수비(含水比) 및 응력수준(應力水準)에 큰 영향(影響)을 받기 때문에 매우 복잡(複雜)하며 따라서 그 거동(擧動)을 해석(解析) 하기도 어려운 일인데 Creep이 궁극적(窮極的)으로는 점토(粘土) 입자간(粒子間)의 미시적(微視的)인 거동(擧動)에서 비롯되기 때문이다. 응력(應力)-변형(變形)-시간(時間) 관계(關係)로서의 Creep 거동(擧動)을 수학적(數學的)으로 표현(表現)하기 위하여 여러 형태(形態)의 유변학적(流變學的) 모델이 제안(提案) 되었다. 유변학적(流變學的) 모델은 선형(線形) 스프링, 비선형(非線形) Dashpot 및 Slider를 조합(組合)한 것인데 점토(粘土)의 변형(變形)에 관한 탄성적(彈性的), 소성적(塑性的) 및 점성적(粘性的) 성분(成分)을 구분(區分) 하는데 매우 유용(有用)하다. 그러나 대부분(大部分)의 경우, 유변학적(流變學的)모델은 포화(飽和)된 점토(粘土)에 대(對)하여 주(主)로 2차압밀(次壓密) 거동(擧動)을 밝히기 위하여 제안(提案)된 것으로 비포화점토(非飽和粘土)에 대(對)한 보고(報告)는 매우 드문 것 같다. 한편, Creep 거동(擧動)은 시간의존변형(時間依存變形)이므로 흐트러진 점토(粘土)를 다져서 시험(試驗)하는 경우, 시간경과(時間經過)에 따라 Thixotropy 문제(問題)가 제기(提起)될 것이고 배수조건(排水條件)과 관련하여서는 공시체(供試體)의 높이가 문제(問題)될 수 있다. 그뿐 아니라 많은 연구결과(硏究結果)에 의(依)하면 응력증가초기(應力增加初期)에는 시간지체(時間遲滯)가 없는 초기탄성변형(初期彈性變形)이 발생(發生)된다고 하므로 유변학적(流變學的) 모델에는 이를 나타내는 요소(要素)가 반드시 필요(必要)하게 될 것이다. 본(本) 연구(硏究)는 이러한 면(面)에 초점(焦點)을 두고 함수비(含水比)와 응력수준(應力水準)을 여러 가지로 변화(變化)시켰을 때의 Creep 거동(擧動)을 유변학적(流變學的) 모델로 해석(解析)함에 있어 소성(塑性)이 비교적(比較的) 큰 3종(種)의 점토(粘土)를 사용(使用)하여 초기탄성변형(初期彈性變形) 거동(擧動)을 밝히고 Thixotropy 효과(効果) 및 공시체(供試體)의 높이가 Creep 거동(擧動)에 끼치는 영향(影響)을 구명(究明)하며 아울러 유변학적(流變學的) 모델의 어떤 요소(要素)에 관련 되는가를 알아내기 위하여 다져서 성형(成形)한 공시체(供試體)로서 일축배수형식(一軸排水形式)의 Creep 거동(擧動)을 시행(施行)하였다. 실험결과(實驗結果) 및 검토(檢討)에 의(依)하면 응력재하(應力載荷) 및 증가초기(增加初期)에는 시간지체(時間遲滯)가 없는 탄성적(彈性的) 초기변형(初期變形)이 발생(發生)하고 따라서 유변학적(流變學的) 모델에는 이를 나타내기 위한 상부(上部)스프링을 설치(設置)해야 하며 Thixotropy 효과(効果)를 고려(考慮)한 경우, Creep변형(變形)은 완만(緩慢)하게 되나 함수비(含水比) 및 응력수준(應力水準)에 따른 상태거동(狀態擧動)은 같으므로 그 차이(差異)는 모델 상수(常數)의 크기에만 관련됨을 알아내었고 따라서 동일(同一)한 유변학적(流變學的) 모델로 그 거동(擧動)을 나타낼 수 있다는 사실(事實)을 밝혀 냈다. 또 공시체(供試體) 높이를 작게 한 경우에는 함수비(含水比)가 비교적(比較的) 작아서 점(粘)-소(塑)-탄성(彈性) 및 점(粘)-탄성(彈性)일 때만 높이가 클 때와 같은 상태거동(狀態擧動)을 나타내어 동일(同一)한 유변학적(流變學的) 모델로 나타낼 수 있고 함수비(含水比)가 큰 점일소성(粘一塑性) 및 점성류(粘性流)일 때는 그 상태거동(狀態擧動)이 배수문제(排水問題)와 관련하여 달라지게 되고 따라서 유변학적(流變學的) 모델도 달라지게 된다는 사실(事實)을 발견(發見) 하였다.