표제지
목차
LIST OF ABBREVIATIONS 10
국문초록 11
I. 서론 13
II. 재료 및 방법 21
1. 시약 및 기기 21
1) 재료 및 시약 21
2) 기기 21
2. 방법 23
1) 표준액 및 검액의 조제 23
2) 방법 24
3) 분석방법의 validation 24
4) 통계분석 28
III. 결과 및 고찰 29
1. 분광학적 분석 29
2. 유연물질 분석방법 validation 36
1) 유연물질 (Related substances) 36
2) 직선성 (Linearity) 36
3) 정확성 (Accuracy) 45
4) 정밀성 (Precision) 45
5) 완건성 (Robustness) 47
6) 특이성 (Specificity) 47
3. 함량 분석방법 validation 53
1) 직선성 (Linearity) 53
2) 정확성 (Accuracy) 53
3) 정밀성 (Precision) 56
4) 특이성 (Specificity) 59
4. 잔류용매 분석방법 validation 59
1) 직선성 (Linearity) 59
2) 정확성 (Accuracy) 72
3) 정밀성 (Precision) 76
4) 완건성 (Robustness) 83
5) 특이성 (Specificity) 87
IV. 결론 91
참고문헌 93
SUMMARY 99
Table 1. List of residual solvents included in the Korea Pharmacopoeia 18
Table 2. HPLC conditions 25
Table 3. GC conditions 26
Table 4. Lists of validation parameters required to be evaluated in tests... 27
Table 5. ¹H-NMR chemical shift assignment for propiverine hydrochloride 32
Table 6. Mass spectrometry assignments for propiverine hydrochloride 34
Table 7. Relationship between benzoin concentration and HPLC peak... 40
Table 8. Relationship between propiverine hydrochloride concentration... 42
Table 9. Accuracy of related substances test by benzoin 46
Table 10. Precision of related substances test by propiverine hydrochloride 48
Table 11. Robustness of related substances test by benzoin 49
Table 12. Robustness of related substances test by propiverine hydrochloride 50
Table 13. Relationship between propiverine hydrochloride weight and... 54
Table 14. Accuracy of content assay test by propiverine hydrochloride 57
Table 15. Precision of content assay test by propiverine hydrochloride 58
Table 16. Specificity of content assay test by propiverine hydrochloride 60
Table 17. Relationship between methanol concentration and GC peak area... 62
Table 18. Relationship between 1-propanol concentration and GC peak... 64
Table 19. Relationship between acetone concentration and GC peak area... 66
Table 20. Relationship between toluene concentration and GC peak area... 69
Table 21. Accuracy of residual solvents test by methanol 73
Table 22. Accuracy of residual solvents test by 1-propanol 74
Table 23. Accuracy of residual solvents test by acetone 75
Table 24. Accuracy of residual solvents test by toluene 77
Table 25. Precision of residual solvents test by methanol 78
Table 26. Precision of residual solvents test by 1-propanol 80
Table 27. Precision of residual solvents test by acetone 81
Table 28. Precision of residual solvents test by toluene 82
Table 29. Robustness of residual solvents test by methanol 84
Table 30. Robustness of residual solvents test by 1-propanol 85
Table 31. Robustness of residual solvents test by acetone 86
Table 32. Robustness of residual solvents test by toluene 88
Fig. 1. Appearance of propiverine hydrochloride powder. 22
Fig. 2. Infrared spectrum of propiverine hydrochloride. 30
Fig. 3. ¹H-NMR spectra of propiverine hydrochloride. 31
Fig. 4. Mass spectra propiverine hydrochloride. 33
Fig. 5. UV/VIS spectrum of propiverine hydrochloride. 35
Fig. 6. TLC of propiverine hydrochloride. 37
Fig. 7. HPLC chromatogram of propiverine hydrochloride. 38
Fig. 8. Calibration curve of related substances test by benzoin. 41
Fig. 9. Calibration curve of related substances test by propiverine hydrochloride. 43
Fig. 10. Relationship beween propiverine hydrochloride and benzoin... 44
Fig. 11. HPLC chromatogram of specificity by related substances test. 52
Fig. 12. Calibration curve of content assay test by propiverine hydrochloride. 55
Fig. 13. Calibration curve of residual solvents test by methanol. 63
Fig. 14. Calibration curve of residual solvents test by 1-propanol. 65
Fig. 15. Calibration curve of residual solvents test by acetone. 68
Fig. 16. Calibration curve of residual solvents test by toluene. 70
Fig. 17. Relationship beween residual solvents concentration from... 71
Fig. 18. GC chromatogram of specificity by residual solvents test. 89