Nuclear Medicine and Molecular Imaging

The Korean Society of Nuclear Medicine (대한핵의학회)
권호 표지

Quality Control of Residual Solvents in $[^{18}F]$FDG Preparations by Gas Chromatography

기체 크로마토그래피를 이용한 $[^{18}F]$FDG 주사액 중의 잔류 용매의 정도관리

  • Lee, Hak-Jeong (Department of Nuclear Medicine, College of Medicine and Institute of Radiation Medicine, Medical Research Center, Seoul National University) ;
  • Jeong, Jae-Min (Department of Nuclear Medicine, College of Medicine and Institute of Radiation Medicine, Medical Research Center, Seoul National University) ;
  • Lee, Yun-Sang (Department of Nuclear Medicine, College of Medicine and Institute of Radiation Medicine, Medical Research Center, Seoul National University) ;
  • Kim, Hyung-Woo (Department of Nuclear Medicine, College of Medicine and Institute of Radiation Medicine, Medical Research Center, Seoul National University) ;
  • Chang, Young-Soo (Department of Nuclear Medicine, College of Medicine and Institute of Radiation Medicine, Medical Research Center, Seoul National University) ;
  • Lee, Dong-Soo (Department of Nuclear Medicine, College of Medicine and Institute of Radiation Medicine, Medical Research Center, Seoul National University) ;
  • Chung, June-Key (Department of Nuclear Medicine, College of Medicine and Institute of Radiation Medicine, Medical Research Center, Seoul National University) ;
  • Lee, Myung-Chul (Department of Nuclear Medicine, College of Medicine and Institute of Radiation Medicine, Medical Research Center, Seoul National University)
  • 이학정 (서울대학교 의과대학 핵의학교실 및 의학연구원 방사선의학연구소) ;
  • 정재민 (서울대학교 의과대학 핵의학교실 및 의학연구원 방사선의학연구소) ;
  • 이윤상 (서울대학교 의과대학 핵의학교실 및 의학연구원 방사선의학연구소) ;
  • 김형우 (서울대학교 의과대학 핵의학교실 및 의학연구원 방사선의학연구소) ;
  • 장영수 (서울대학교 의과대학 핵의학교실 및 의학연구원 방사선의학연구소) ;
  • 이동수 (서울대학교 의과대학 핵의학교실 및 의학연구원 방사선의학연구소) ;
  • 정준기 (서울대학교 의과대학 핵의학교실 및 의학연구원 방사선의학연구소) ;
  • 이명철 (서울대학교 의과대학 핵의학교실 및 의학연구원 방사선의학연구소)
  • Published : 2007.12.31
Download PDF
⟨ Previous Next ⟩

Abstract

Purpose: Analysis of volatile organic solvents in 2-deoxy-2-$[^{18}F]$ fluoro-D-glucose ($[^{18}F]$FDG) preparations was performed by gas chromatography (GC), in accordance with USP. Materials and Methods: Analyses were carried out on a Hewlett-Packard 6890 gas chromatography equipped with an FID. Results: We determined the amounts of ethanol and acetonitrile on every batch of our routine $[^{18}F]$FDG preparations, ranging between 5000 ppm and 100 ppm. In our routine preparation of $[^{18}F]$FDG, the amount of acetonitrile and ethanol in the final product were well below the maximum allowable limit described in the USP. Conclusion: Our $[^{18}F]$FDG preparations were in accordance with the suggested USP maximum allowable levels of the quality control analysis of volatile organic compounds.

목적: 의약품의 FDA 개정에 따라 $[^{18}F]$FDG에 휘발성 유기 용매의 분석을 GC로 수행하였다. $[^{18}F]$FDG 주사액은 약 3개월에 걸쳐 생산하면서 정도관리를 수행하였다. 대상 및 방법: $[^{18}F]$FDG 주사액에 존재하는 잔류유기용매의 종류를 줄이기 위해 $[^{18}F]$FDG자동합성장치를 ethanol을 이용해 세정하였다. $[^{18}F]$FDG주사액은 FID가 장착된 Hewlett-Packard 6890 Gas Chromatograph로 분석을 수행하였다. 생산된 $[^{18}F]$FDG의 시료는 상온에서 밀봉된 Vial에 보관하였고 일주일 내에 분석하였다. 결과: $[^{18}F]$FDG 생성물에서 ethanol의 양은 $16.8\sim2762.8ppm$이 검출 되었고 acetonitrile의 양은 $2.3\sim327.6ppm$이 검출 되었다. 결론: 약 3개월간 생산한 $[^{18}F]$FDG 주사액 중에 ethanol과 acetonitrile잔류 용매를 측정해본 결과 USP 허용기준인 ethanol 5000 ppm과 acetonitrile 400 ppm 이하가 유지됨을 확인하였다.

Keywords

References

  1. Alexoff DL, Casati R, Fowler JS, Wolf AP, Shea C, Schlyer DJ, et al. Ion Chromatographic Analysis of High Specific Activity $^{18}$FDG Preparations and Detection of the Chemical Impurity 2-Deoxy-2-chloro-D-glucose. Appl Radiat Isot 1992;43:1313-22 https://doi.org/10.1016/0883-2889(92)90002-V
  2. Alexoff DL, Fowler JS, Gatley SJ. Removal of the 2.2.2 Cryptand (Kryptofix 2.2.2) from $^{18}$FDG by Cation Exchange. Appl Radiat Isot 1989;42:1189-93
  3. Chaly T, Dahl JR. Thin layer Chromatographic Detection of Kryrtofix 2.2.2 in the Routine Synthesis of [$^{18}$F]2-Fluoro-2-deoxy- Dglucose. Nucl Med Biol 1989;16:385-7
  4. Ferrieri RA, Schlyer DJ, Alexoff DL, Fowler JS, Wolf AP, Direct Analysis of Kryptofix 2.2.2 in $^{18}$FDG by Gas Chromatography Using a Nitrogen-selective Detector. Nucl Med Biol 1993;20:367-9 https://doi.org/10.1016/0969-8051(93)90061-X
  5. Mock BH, Winkle W, Vavrek MT. A Color Spot Test for the Detection of Kryptofix 2.2.2 in [$^{18}$F]FDG Preparations. Nucl Med Biol 1997;24:193-5 https://doi.org/10.1016/S0969-8051(96)00212-0
  6. Moerlein SM, Brodack JW, Siegel BA, Welch MJ. Elimination of Contaminant Kryptofix 2.2.2 in the Routine Production of 2-[$^{18}$F]Fluoro-2-deoxy-D-glucose. Appl Radiat Isot 1989;40:741-3 https://doi.org/10.1016/0883-2889(89)90090-7
  7. Channing MA, Huang BX, Eckelman WC. Analysis of residual solvents in 2-[$^{18}$F]FDG by GC. Nucl Med Biol 2001;28:469-71 https://doi.org/10.1016/S0969-8051(00)00213-4
  8. Hung JC. Comparison of Various requirements of the Quality Assurance procedures for $^{18}$F-FDG Injection. J Nucl Med. 2002;43: 1495-1506
  9. Yu S. Review of $^{18}$F-FDG synthesis and Quality control. Biomed Imaging Interv J 2006;2(4):e57
  10. Rockville, MD. Organic volatile impurities. (2000)The United States Pharmacopeia 24/National Formulary 19 The United States Pharmacopeial Convention
  11. Hamacher K, Coenen HH, Stcklin G. Efficient Stereospecific Synthesis of No-Carrier-Added 2-[$^{18}$F]-Fluoro-2-Deoxy-D-Glucose Using Aminopolyether supported Nucleophilic Substitution, J Nucl Med 1986;27:235-8
  12. Chang IL, Diubaldo D, Sanders WJ. Headspace Analysis of Organic Volatile Impurities in Bulk Pharmaceutical Chemicals. Hewlett-Packard Company, USA, 1994 Application Note 228-55
  13. Classification of residual solvents by risk assessment. In: Guidance for Industry: Q3C Impurities-Residual Solvents. Rockville, MD: Food and Drug Administration; 1997:3 Available at: http://www.Fda.gov/cder/guidance/Q3Cfnl.pdf. Accessed August 14, 2002
  14. The Merck Index 13th edition, An Encyclopedia of Chemicals, Drugs. And Biologicals. Maryadele J. O'Neil et al (Ed.). Whitehouse Station. Nj. Merck & Co., Inc. 2001
  15. Acetonitrile [material safety data sheet]. Thermo Fisher Scientific Inc. available USA at: http://fscimage.fishersci.com/msds/00170.html. Accessed June 19, 2007
  16. Ethanol SDA1, Anhydrous [material safety data sheet]. Thermo Fisher Scientific Inc. USA. available at: http://fscimage.fishersci.com/msds/88067.html. Accessed June 19, 2007