Development of certified reference materials of pesticides and their metabolites using mass balance method and differential scanning calorimetry : Isofetamid, GPTC, Tiafenacil, Imidacloprid, and Cyclaniliprole
- 주제(키워드) Pesticide , Metabolite , Certified reference material , Mass balance method , Differential scanning calorimetry , Uncertainty
- 주제(DDC) 615.1
- 발행기관 아주대학교
- 지도교수 백승훈
- 발행년도 2023
- 학위수여년월 2023. 2
- 학위명 석사
- 학과 및 전공 일반대학원 약학과
- 실제URI http://www.dcollection.net/handler/ajou/000000032533
- 본문언어 영어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
Expansion of population due to steady economic growth and urbanization worldwide has facilitated the development and use of pesticides for food production. The active ingredients of pesticides and their metabolites which reside in agricultural foods may induce the harmful effects on the human health. To ensure the food safety from pesticide residue, maximum residue limits were established and regulated for each pesticide and metabolite in food. Certified reference materials (CRMs) play critical roles in the reliable measurement result of pesticide residue and the decision of legislative limits related to the distribution of food. This study aims to develop the CRMs for pesticides and metabolites including isofetamid, GPTC a metabolite of isofetamid, tiafenacil, imidacloprid, and cyclaniliprole. Certification of processes included the characterization, homogeneity, stability, and uncertainty according to ISO guide 35:2017. For characterization, the mass balance method and the differential scanning calorimetry were performed to cross-check and supplement each other. Organic impurities were measured using HPLC-UV. Inorganic impurities, water, and residual solvents were measured by the residue on ignition, the Karl Fischer titration, and residual solvent assay following the Korean Pharmacopoeia. Homogeneity and stability studies were conducted to ensure the reliability of CRMs. The stability studies were carried out in terms of long-term and short-term with the different packaging conditions. Candidate CRMs were homogenous and stable for all conditions. The combined uncertainty was calculated from characterization, homogeneity, and stability, and the expanded uncertainty was estimated by obtaining the coverage factor (k) at the 95% confidence level from the effective degrees of freedom. The purity ± expanded uncertainties of 5 CRMs were 99.31% ± 0.30% for isofetamid, 98.03% ± 0.82% for GPTC, 98.54% ± 0.40% for tiafenacil, 98.73% ± 0.14% for imidacloprid, and 97.58% ± 0.92% for cyclaniliprole. This study can contribute to the stable supply of established CRMs to the national testing agencies and reliable analysis results in the pesticide residue analysis.
more초록/요약
전 세계적으로 꾸준한 경제 성장과 도시화로 인한 인구 증가는 식량 생산을 위한 농약의 개발과 사용을 촉진시켰다. 농산물에 존재하는 농약의 활성 성분과 그 대사체는 인체 건강에 유해한 영향을 줄 수 있다. 잔류 농약으로부터 식품 안전을 보장하기 위해 식품의 각 농약 및 대사체에 대해 최대 잔류 허용 기준을 설정하여 규제하고 있다. CRM (Certified Reference Material)은 신뢰할 수 있는 잔류 농약 측정 결과와 식품 유통과 관련된 법적 한계치 결정에 중요한 역할을 한다. 본 연구는 isofetamid, 그 대사체인 GPTC, tiafenacil, imidacloprid 및 cyclaniliprole을 포함한 농약 및 대사체에 대한 CRM을 개발하는 것을 목표로 한다. CRM의 인증에는 ISO 가이드 35:2017에 따른 특성화, 균질성, 안정성 및 불확도가 포함된다. 특성화를 위해 mass balance 법과 시차주사열량법을 수행하여 서로 교차 확인하고 보완하였다. 유기 불순물은 HPLC-UV를 사용하여 측정하였다. 무기불순물, 수분, 잔류용매는 대한약전에 따라 강열잔분법, 칼피셔적정법, 잔류용매법으로 측정하였다. CRM의 신뢰성을 확보하기 위해 균질성 및 안정성 연구를 수행하였다. 안정성 연구는 다양한 포장 조건에서 장기 및 단기 안정성 평가를 수행하였다. 후보 CRM은 모든 조건에서 균질하였고, 안정하였다. 합성 불확도는 특성화, 균질성, 안정성으로부터 계산하였고, 확장 불확도는 95% 신뢰수준에서 유효자유도로부터 coverage factor (k)를 구하여 추정하였다. 5개 CRM의 순도 ± 확장 불확도는 isofetamid의 경우 99.31% ± 0.30%, GPTC의 경우 98.03% ± 0.82%, tiafenacil의 경우 98.54% ± 0.40%, imidacloprid의 경우 98.73% ± 0.14%, cyclaniliprole의 경우 97.58% ± 0.92%였다. 본 연구는 국가 시험기관에 확립된 CRM을 안정적으로 공급하고 잔류농약 분석에서 신뢰할 수 있는 분석 결과에 기여할 수 있을 것이다.
more목차
1. Introduction 1
1.1. Certified reference material (CRM) 1
1.2. Pesticide residue 3
1.3. Mass balance method for the purity of CRMs 5
1.4. Target pesticides or metabolites for CRM in this study 7
1.4.1. Isofetamid and GPTC 7
1.4.2. Tiafenacil 8
1.4.3. Imidacloprid 9
1.4.4. Cyclaniliprole 9
1.5. Aims of this study 10
2. Experimental 11
2.1. Reagents 11
2.2. Balance 11
2.3. Candidate materials for CRM 12
2.4. Subdivision and and packaging of candidate CRMs 12
2.5. Mass balance method for purity determination 13
2.5.1. Organic impurity assay using high performance liquid chromatography 13
2.5.2. Water content assay using Karl-Fischer coulometric titration 15
2.5.3. Inorganic impurity assay using residue on ignition 15
2.5.4. Residual solvent assay using GC-MS 16
2.5.5. Purity calculation 17
2.6. Differential scanning calorimetry (DSC) for purity determination 19
2.7. Homogeneity study 21
2.8. Stability study 22
3. Results and discussion 24
3.1. Purity determination using mass balance method 24
3.1.1. Organic impurities assessed using HPLC 24
3.1.2. Residual solvents assessed using GC-MS 27
3.1.3. Purity calculation of candidate CRMs 32
3.2. Purity determination using DSC 34
3.3. Homogeneity study 42
3.4. Stability study 48
3.5. Uncertainty estimation 56
3.5.1. Uncertainty of mass balance method 56
3.5.2. Uncertainty of differential scanning calorimetry (DSC) 61
3.5.3. Uncertainty of characterization and calculation of final purity combining the results of mass balance and DSC method 63
3.5.4. Uncertainty of homogeneity 64
3.5.5. Uncertainty of stability 65
3.5.6. Combined and expanded uncertainty 65
Acknowledgements 71
References 72
