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2012 2013 2014 R&D 예산 1,400 백만원 1,576 백만원 1,854 백만원 제조표준품품목수 56 80 81-14 -
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α 테프론으로코팅한황갈색바이알 ( 대한약전표준품및화학표준물질의대표적용기 ) 을사용한다 3) 포장은질소충전하에항온항습실내에서실시한다. - 27 -
1 품목명 디히드로코데인 타르타르산염 관리 번호 MFDS 07-01 MFDS 09-01 2 레미펜타닐염산염 MFDS 12-02 MFDS 3 4 모르핀염산염수화물 모르핀황산염수화물 10-01 KFDA 06-02 MFDS 06-03 MFDS 10-02 5 수펜타닐시트르산 MFDS 05-05 6 알펜타닐염산염 MFDS 05-01 7 옥시코돈 MFDS 12-10 MFDS 8 9 옥시코돈염산염수화물 코데인인산염수화물 10 페티딘염산염 11 펜타닐 12 펜타닐시트르산염 13 14 히드로모르폰염산염 히드로코돈타르타르산염 15 날부핀염산염 10-03 KFDA 07-14 MFDS 10-04 MFDS 10-05 MFDS 12-17 MFDS 05- MFDS 09-02 MFDS 07-04 MFDS 09-03 MFDS 06-01 MFDS 07-13 MFDS 10-06 MFDS 12-01 보유량 2003 2005 2006 2007 2008 2009 2010 2012 (dried) 2013 2014 대상 근거 ( 시험대상제외시 ) 1.3 98.7 98.9 99.4 x 보유양적음 6.3 99.4 99.5 o 15.1 99.6(M) 99.7(H) 7.5 100.4 100.6 x 2013 년재시험완료 0.1 100.3 100.4 100.1 x 2013 년재시험완료 1.6 99.5 98.3 97.5 x 2013 년재시험완료 8.6 100.2 100.6 x 2013 년재시험완료 0.1 100.4 100.5 100.1 96.2 x 보유양적음 0.6 99.7 98.4 98.5 20 97.3 (100.1) 99.8(M) 100.2(T) o x o 보유양적음 7.3 99.9 100.2 x 2013 년재시험완료 0.2 100.8 100.1 94.6 (100.6) x 보유양적음 6.4 99.8 100.1 x 2013 년재시험완료 7.2 99.8 100.3 x 2013 년재시험완료 25.2 99.8(M) 100.5(T) 99.8 99.8 99.6 100.7 x 3.1 99.9 100.5 x o 05 년표준품 7 년간 안정성확보 05년표준품 7년간 안정성확보 1.9 100.4 100.5 100.0 x 보유양적음 7.6 100.2 99.8 o 8.9 100.4 100.4 99.9 x 2013 년재시험완료 12.7 100.1 98.7 99.2 o 9.4 99.0 99.8 x 2013 년재시험완료 11.9 95.2(M), 95.6(T) o - 28 -
16 노르펜플루라민염산염 MFDS 10-07 -1 MFDS 10-07 -2 17 덱스트로메토르판 MFDS 브롬화수소산염 03-04 18 디아제팜 MFDS 07-12 19 디에틸프로피온 MFDS 염산염 08-03 20 로라제팜 MFDS 07-06 21 마진돌 MFDS 12-03 22 메타콰론 MFDS 09-04 23 메탐페타민염산염 MFDS 10-08 24 메틸페니데이트 MFDS 염산염 08-06 25 멕사졸람 MFDS 12-04 26 미다졸람 MFDS 08-11 27 벤질피페라진 MFDS 염산염 09-05 28 브로마제팜 MFDS 09-06 29 알프라졸람 MFDS 06-08 30 암페타민 MFDS 10-09 31 암페타민황산염 MFDS 10-10 32 에스타졸람 MFDS 09-07 33 에티졸람 MFDS 12-05 34 에틸로플라제 MFDS 페이트 12-06 35 엠디비피염산염 MFDS 09-08 MFDS 36 엠디엠에이염산염 37 38 제이더블유에이치 -018 졸피뎀타르타르산염 39 지에이치비 40 카리소프로돌 41 클로나제팜 03-03 MFDS 12-09 MFDS 12-11 MFDS 09-09 MFDS 09-10 MFDS 03-05 MFDS 05-03 MFDS 09-11 1.7 99.9 98.1 x 2013 년재시험완료 7.9 99.7 x 2013 년재시험완료 3.9 100.4 101.8 101.9 99.8 100.1 x 2013 년재시험완료 12 99.8 99.9 100.6 o 10.4 99.3 102.1 99.5 x 2013 년재시험완료 14.6 98.5 98.6 100.1 o 10 99.0(M) 99.6(T) 8 99.9 97.5 o 7.6 99.7 100.1 x 2013 년재시험완료 8.4 99.7 99.1 100 x 2013 년재시험완료 8.8 99.8(M) 100.2(T) 11.3 100.8 100.4 99.1 x 2013 년재시험완료 9.1 100.0 99.8 o 5.3 99.9 100.3 o 0 99.7 99.5 99.7 x 2013 년재시험완료 2.0 99.9 99.5 x 2013 년재시험완료 9.7 99.9 100 x 2013 년재시험완료 5.5 99.4 100.1 o 9.9 14.2 99.8(M) 99.9(T) 99.6(M) 100.5(T) 10.4 99.7 99.7 o 4.3 100.1 99.7 101.2 99.9 98.9 x 2013 년재시험완료 25.8 11 98.5(M) 98.8(H) 99.6(M) 99.7(H) 5.4 100.1 100.1 o 9.2 99.9 99.9 o 7.3 100.5 99.8 100.0 99.8 99.5 x 2013 년재시험완료 0.2 100.0 100.4 101.8 100.0 x 보유양적음 4.6 99.8 100.0 x o o o o o o 05 년표준품 7 년간 안정성확보 - 29 -
42 클로라제페이트 MFDS 98.9(M) 10.7 디칼륨 12-12 100.1(T) o 43 클로르디아제폭시 MFDS 9.8 99.9(M) 드 12-13 99.9(T) o 44 클로르디아제폭시 MFDS 05년표준품 7년간 3.5 99.7 98.6 98.4 99.9 x 드염산염 05-02 안정성확보 45 클로바잠 MFDS 08-01 14.8 100.5 99.0 99.5 x 2013년재시험완료 46 클로티아제팜 MFDS 99.6(M) 10.1 12-14 100.4(T) o 47 테마제팜 MFDS 09-13 6.0 99.4 100.1 o 48 트리아졸람 MFDS 10-11 5 101.4 99.4 x 2013년재시험완료 49 페노바르비탈 MFDS 07-09 10.4 99.6 99.5 99.5 o 50 MFDS 1.2 99.6 100.0 100.2 x 2013년재시험완료펜디메트라진타르 08-08 타르산염 MFDS 99.4(M) 8.6 12-15 100.4(T) o 51 펜메트라진염산염 MFDS 99.8(M) 13.2 12-16 100.4(U) o 52 펜타조신 MFDS 08-07 6.9 99.1 100.0 100.1 x 2013년재시험완료 53 펜터민염산염 MFDS 10-12 5.5 99.1 99.2 x 2013년재시험완료 54 펜토바르비탈 MFDS 10-13 7.8 99.8 99.7 x 2013년재시험완료 55 펜푸르라민염산염 MFDS 03-01 5.5 99.2 101.5 100.6 100.5 100.9 x 2013년재시험완료 56 프로포폴 MFDS 12.6 99.9(M) 12-18 100.0(H) o 57 플루니트라제팜 MFDS 09-12 4.2 99.9 100.2 o 58 플루라제팜염산염 MFDS 10-14 7.3 100.5 100.2 x 59 헥소바르비탈 MFDS 07-03 14.7 99.8 99.7 99.2 o 60 엠이오피피 MFDS 10-15 9.5 99.8 99.8 x 2013년재시험완료 61 2씨아이염산염 MFDS 08-02 8.8 99 99.8 98.8 x 2013년재시험완료 62 3-히드록시벤질피 MFDS 페라진염산염 10-16 5.6 99.9 99.0 x 2013년재시험완료 63 4-히드록시벤질피 MFDS 페라진염산염 10-17 3.6 99.9 99.1 x 2013년재시험완료 64 5-메오딥트염산염 MFDS 08-05 7 99 99.3 99.5 x 2013년재시험완료 65 (-)-델타테트라히 MFDS 드로칸나비놀 10-18 1.1 95.2 73.5 x 2013년재시험완료 66 수도에페드린 MFDS 염산염 08-09 2.4 100.5 100.3 99.9 x 2013년재시험완료 67 에페드린염산염 MFDS 7.2 99.9(M) 12-07 99.6(T) o 68 에페드린황산염 MFDS 11.2 99.7(M) 12-08 98.9(T) o - 30 -
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- 재검증목적은표준품의계속사용적합성을보장하기위한재시험주기및범위를확립하기위한것이다. 보유하고있는표준품의양을고려하여재검증시험항목을최소화하였다. 제조당시및이전년도에비하여정량및총유연물질이유의적인함량변화가있는지에대하여안정성결과를확인하였다. - 32 -
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μ - 39 -
μ μ - 40 -
IR (KBr) 3293 cm -1 : N + -H 3089 cm -1 : sp 2 C-H 3053 cm -1 : sp 2 C-H 2991 cm -1 : sp 3 C-H 2928 cm -1 : sp 3 C-H 2856 cm -1 : sp 3 C-H - 41 -
* solvent : NMR 측정용으로쓰인 (CD 3) 2SO 에미량혼재된 (CH 3) 2SO 의피크 - 42 -
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μ - 48 -
μ μ - 49 -
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D 2O (NMR 측정용 ) D 2O에녹여 400 MHz NMR에서 1 H-NMR spectrum을측정하였다. 30 mg을 D 2O에녹여 100 MHz NMR에서 13 C-NMR spectrum을측정하였다. - 54 -
μ μ - 55 -
IR (KBr) - 3277 cm -1 : N-H 3013 cm -1 : sp 2 C-H 2937 cm -1 : sp 3 C-H 2866 cm -1 : sp 3 C-H 2801 cm -1 : sp 3 C-H 1037 cm -1 : C-O - 56 -
* water : NMR 측정에사용한 D 2O 에미량혼재된 H 2O 의피크. 혹은시료화합물의 proton 이 D 2O 의 deuterium 과치환되어나타나는피크 - 57 -
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μ μ - 60 -
Ephedrine HCl) - 61 -
ystem suitability - 62 -
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CDCl 3 에녹여 400 MHz NMR에서 1 H-NMR spectrum을측정하였다. 30 mg을 CDCl 3 에녹여 100 MHz NMR에서 13 C-NMR spectrum을측정하였다. - 66 -
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μ μ - 68 -
IR (KBr) - 3015 cm -1 : sp 2 C-H 3060 cm -1 : sp 2 C-H 1618 cm -1 : C=N - 69 -
* water : NMR 측정에사용한용매에미량혼재되어있는수분, 혹은공기중의수분이 NMR 측정시료에 혼입되어나타나는피크 * solvent : NMR 측정용으로쓰인 CDCl 3 에미량혼재된 CHCl 3 의피크 - 70 -
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μ μ μ - 73 -
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5 mg 을 CD 3OD에녹여 400 MHz NMR에서 1 H-NMR spectrum 을측정하였다. 30 mg을 CD 3OD에녹여 100 MHz NMR에서 13 C-NMR spectrum 을측정하였다. - 79 -
μ - 80 -
μ μ - 81 -
IR (KBr) - 3452 cm -1 : N + -H 3080 cm -1 : sp 2 C-H 2922 cm -1 : sp 3 C-H 1640 cm -1 : C=O - 82 -
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μ μ 1 2 3 4 5 6 7-88 -
ystem suitability - 89 -
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μ μ - 98 -
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μ μ - 103 -
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μ μ - 107 -
r 2-108 -
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μ - 112 -
r 2-113 -
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μ μ Time(min) A B 0-15 80 20 15-30 80 70 20 30 30-40 70 40 30 60 40-42 40 60 r 2-117 -
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μ μ - 123 -
r 2-124 -
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μ μ - 128 -
r 2-129 -
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μ μ - 134 -
r 2-135 -
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μ μ r 2-139 -
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μ μ - 144 -
r 2-145 -
ystem suitability System suitability Specification Results Resolution 4 (bromazepan & imp.d) 9.45 1.2 (imp.a & imp.c) 1.21-146 -
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μ μ - 150 -
r 2-151 -
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μ μ r 2-155 -
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μ μ - 160 -
r 2 1 2 3 4 5 6 7-161 -
ystem suitability System suitability Specification Results Resolution 9.45 Reproducibility 1.66-162 -
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μ r 2-166 -
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μ μ - 171 -
r 2 45000 36000 27000 a re A 18000 y = 20.3602X + 140.0275 R² = 0.9999 1 차 2 차 3 차 9000 0 0 500 1000 1500 2000 2500 Conc(ug/mL) - 172 -
ystem suitability System suitability Specification Results Resolution 10.13-173 -
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μ μ Time(min) A B C 0-18 54 39 7 18-25 54 22 39 63 7 15 25-31 22 63 15 31-37 22 54 63 39 15 7-177 -
r 2-178 -
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μ μ - 182 -
r 2-183 -
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μ μ r 2-187 -
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μ μ - 197 -
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μ μ - 202 -
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System suitability Specification Results Fig 2. HPLC chromatogram of resolution test - 204 -
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μ μ - 208 -
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μ μ - 213 -
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Fig 2. HPLC chromatogram of resolution test Fig 3. HPLC chromatogram of sensitivity test - 215 -
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μ μ - 219 -
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Fig 2. HPLC chromatogram of resolution test Fig 3. HPLC chromatogram of sensitivity test - 221 -
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μ - 225 -
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μ A B μ - 230 -
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μ μ - 235 -
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μ μ - 240 -
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μ μ - 244 -
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μ 260 280 300 μ - 249 -
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μ μ - 254 -
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μ μ - 259 -
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μ A B μ - 264 -
Fig 1. HPLC chromatogram of resolution test - 265 -
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μ μ Propofol - 269 -
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Propofol Propofol - 271 -
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μ μ - 277 -
r 2-278 -
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μ μ - 283 -
r 2-284 -
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μ μ - 289 -
r 2-290 -
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μ A B μ - 295 -
r 2-296 -
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μ μ - 301 -
r 2-302 -
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μ μ - 307 -
r 2-308 -
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μ μ - 313 -
r 2-314 -
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μ μ - 319 -
r 2-320 -
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μ μ - 325 -
r 2-326 -
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μ μ - 331 -
r 2-332 -
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μ μ - 337 -
r 2-338 -
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220 20 /min 300 (28 min) 270 300 r 2-343 -
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