Development of a novel deproteinization method to improve recovery efficiency : an application to pharmacokinetic study of Ellagic acid|RISS 상세보기

목차 (Table of Contents)

List of Table Ⅳ
List of Figure Ⅴ
Abstract Ⅶ

List of Table Ⅳ
List of Figure Ⅴ
Abstract Ⅶ
국문요약 Ⅸ
Ⅰ. 이론적 배경 1
1. ELLAGIC ACID (EA) 1
1.1. EA의 물리화학적 특성 1
1.2. EA의 흡수, 분포, 대사, 배설 2
1.3. EA의 생체 시료 분석법 요약 2
1.4. EA의 낮은 제단백 효율 3
2. 제단백 3
2.1. SPE 3
2.2. 단백질 침전법 3
3. LC-MS/MS 4
4. IN VIVO 약동학 연구 4
Ⅱ. 서론 5
Ⅲ. 연구 방법 6
1. 시약 및 재료 6
2. EA의 개선된 제단백 방법 6
2.1. SPE 6
2.2. 단백질 침전법 7
2.3. 회수율의 계산 8
3. LC 분석 조건의 최적화 8
4. 표준원액 및 표준용액 조제 8
5. 생체 시료의 전처리 9
6. 분석법 밸리데이션 9
6.1. 규제 당국 가이던스 9
6.2. 분석법 부분 밸리데이션 9
6.3. 시험 내 분석에서의 정밀성과 정확성 10
6.4. 최저정량한계 10
6.5. 표준검량선의 선형성 10
7. IN VIVO 연구 11
7.1. 동물 11
7.2. 동물 수술 11
7.3. 투여용매 제조 11
7.4. 투여 및 채혈 12
7.5. 데이터 분석 및 통계처리 12
Ⅳ. 연구결과 13
1. 제단백 방법 연구 13
1.1. SPE 13
1.2. 단백질 침전법 14
2. LC-MS/MS 분석법 개발 16
2.1. 이동상 선정 16
2.2. LC 분석조건 17
2.3. Mass spectrometry 및 LC 분석 조건 확립 18
2.4. 분석법 밸리데이션 19
3. IN VIVO 연구 22
Ⅴ. 고찰 26
Ⅵ. 요약 및 결론 28
Ⅶ. 참고문헌 29
List of Table
TABLE 1 THE ADDITION OF H₃PO₄ AND KH₂PO₄, FOLLOWED BY
SOLID-PHASE EXTRACTION, DID NOT LEAD TO A SIGNIFICANT
IMPROVEMENT IN PROTEIN DEPROTEINIZATION EFFICIENCY. 14
TABLE 2 WITHIN-RUN PRECISION AND ACCURACY OF QC SAMPLES FOR
EA IN RAT PLASMA 20
TABLE 3 WITHIN-RUN PRECISION AND ACCURACY OF QC SAMPLES FOR
EA IN MOUSE PLASMA 21
TABLE 4 IN A RAT PHARMACOKINETIC STUDY, 0.16% FA WAS USED IN
ALL PLASMA SAMPLES TO IMPROVE PROTEIN DEPROTEINIZATION
EFFICIENCY. 23
TABLE 5 IN A MOUSE PHARMACOKINETIC STUDY, 1% FA WAS USED IN
ALL PLASMA SAMPLES TO IMPROVE PROTEIN DEPROTEINIZATION
EFFICIENCY. 25
List of Figure
FIGURE 1 EA 구조 1
FIGURE 2 THE P VALUE OF EA AND A IS LESS THAN 0.0001,
INDICATING STATISTICAL SIGNIFICANCE, WHILE THE P VALUE OF
EA AND B IS 0.0391. THE STARS INDICATE STATISTICAL
SIGNIFICANCE: *P < 0.05. (DUNNETT'S MULTIPLE COMPARISONS
TEST) 13
FIGURE 3 THE STATISTICAL P VALUES OF H₃PO₄, ACETIC ACID AND
FA ARE LESS THAN 0.001, INDICATING STATISTICAL
SIGNIFICANCE 15
FIGURE 4 THE STATISTICAL P VALUES OF 1% FA AND FA ARE LESS
THAN 0.0001, INDICATING STATISTICAL SIGNIFICANCE, WHILE THE
P VALUE OF EA AND 5% FA IS 0.0279. 15
FIGURE 5 RUN TIME 7MIN CHROMATOGRAM OF EA WITH AND WITHOUT
0.1% FA IN 이동상 (0.1% FA IN DISTILLED WATER-ACN) 16
FIGURE 6 RUN TIME 7MIN CHROMATOGRAMS OF EA WITH 0.1% FA IN 이
동상 (0.1% FA IN DDW- 0.1% FA IN ACN) 16
FIGURE 7 RUN TIME 4MIN CHROMATOGRAMS OF EA WITH 0.1% FA IN 이
동상 (0.1% FA IN DDW- 0.1% FA IN ACN) 17
FIGURE 8 CHROMATOGRAM OF EA UNDER GRADIENT CONDITIONS 17
FIGURE 9 CHROMATOGRAM OF EA UNDER ISOCRATIC CONDITIONS 18
FIGURE 10 RAT PLASMA CONCENTRATION PROFILES AFTER
INTRAVENOUS ADMINISTRATION OF EA AT THE DOSE OF 5MG/KG
(N=3) (MEAN±SD). INSET: SEMI-LOG PLOT OF PLASMA
CONCENTRATION PROFILES. 22
FIGURE 11 RAT PLASMA CONCENTRATION PROFILES AFTER ORAL
ADMINISTRATION OF EA AT THE DOSE OF 50MG/KG (N=3) (MEAN±
SD). 23
FIGURE 12 MOUSE PLASMA CONCENTRATION PROFILES AFTER
INTRAVENOUS ADMINISTRATION OF EA AT THE DOSE OF 5MG/KG
(N=4) (MEAN±SD). INSET: SEMI-LOG PLOT OF PLASMA
CONCENTRATION PROFILES. 24
FIGURE 13 MOUSE PLASMA CONCENTRATION PROFILES AFTER ORAL
ADMINISTRATION OF EA AT THE DOSE OF 50MG/KG (N=4) (MEAN±
SD). 24

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Development of a novel deproteinization method to improve recovery efficiency : an application to pharmacokinetic study of Ellagic acid

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