[en] A fast headspace GC-MS method was developed and validated for the detection and quantification of residual solvents of all three ICH-classes in counterfeit tablets and capsules. The method was validated for ten solvents, selected based on an initial screening of counterfeit medicinal products. The considered solvents were ethanol, 2-propanol, acetone, ethylacetate, chloroform, carbon tetrachloride, benzene, toluene, dichloromethane and ethylbenzene. The proposed method uses a Phenomenex 624 capillary column (60 m x 0.32 mm; 1.8 µm film thickness) (Phenomenex, Torrance, USA) with an oven temperature program from 60°C (held for 5 min) to 270°C at 25 °C/min. 270°C is held for 10 min. The total run time is 23.4 minutes.
The obtained method was fully validated by applying the “total error” profile. Calibration lines for all components were linear within the studied ranges. The relative bias and the relative standard deviations for all components were smaller than 5%, the -expectation tolerance limits did not exceed the acceptance limits of 10% and the relative expanded uncertainties were acceptable for all of the considered components.
A method was obtained for the screening and quantification of residual solvents in counterfeit tablets and capsules, which will allow a fast screening of these products for the presence of residual solvents.
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Deconinck, Eric
Canfyn, Michaël
Sacre, Pierre-Yves ; Université de Liège - ULiège > Département de pharmacie > Chimie analytique
Baudewyns, Sébastien
Courselle, Patricia
De Beer, Jacques O.
Language :
English
Title :
A validated GC-MS method for the determination and quantification of residual solvents in counterfeit tablets and capsules
International Conference on Harmonisation (ICH) of Technical Requirements for the Registration of Pharmaceuticals for Human Use, Q3C: impurities: Guidelines for Residual Solvents, Step 4, 1997.
United States Pharmacopoeia 35 2010, United States Pharmacopeial Convention, Inc., Rockville, MD, USA.
European Pharmacopoeia, 7.0 2010, Council of Europe, Strasbourg, France.
Japanese Pharmacopoeia 2011, Society of Japanese Pharmacopoeia, Tokyo. 16th ed.
Grodowska K., Parczewski A. Organic solvents in the pharmaceutical industry. Acta Pol. Pharm. 2010, 67:3-12.
Grodowska K., Parczewski A. Analytical methods for residual solvents determination in pharmaceutical products. Acta Pol. Pharm. 2010, 67:13-26.
D'Autry W., Zheng C., Wolfs K., Yarramraju S., Hoogmartens J., Van Schepdael A., Adams E. Mixed aqueous solutions as dilution media in the determination of residual solvents by static headspace gas chromatography. J. Sep. Sci. 2011, 34:1299-1308.
D'Autry W., Zheng C., Bugalama J., Wolfs K., Hoogmartens J., Adams E., Wang B., Van Schepdael A. Liquid paraffin as new dilution medium for the analysis of high boiling point residual solvents with static headspace-gas chromatography. J. Pharm. Biomed. Anal. 2011, 55:1017-1023.
D'Autry W., Wolfs K., Hoogmartens J., Adams E., Van Schepdael A. Improving quantitative gas chromatography-electron ionization mass spectrometry results using a modified ion source: demonstration for a pharmaceutical application. J. Chromatogr. A 2011, 18:4034-4038.
Weiss A. Buying prescription drugs on the Internet: promises and pitfalls. Cleve. Clin. J. Med. 2006, 73:282-288.
Veronin M., Youan B.-B. Magic bullet gone astray: medications and the Internet. Science 2004, 305:481.
European Alliance For Access to Safe Medicines: http://www.eaasm.eu/.
WHO, sixty-second world health assembly item 12.9, counterfeit medical products, April 2009. http://aps.who.int/gb/ebhwa/pdf_files/A62/A62_13-en.pdf.
Sacré P.Y., Deconinck E., Chiap P., Crommen J., Rozet E., Courselle P., De Beer J.O. Development and validation of a UHPLC-UV method for the detection and quantification of erectile dysfunction drugs and some of their analogues found in counterfeit medicines. J. Chromatogr. A 2011, 1218:6439-6447.
Deconinck E., Verlinde K., Courselle P., De Beer J. A validated Ultra High Pressure Liquid Chromatographic method for the characterisation of confiscated illegal slimming products containing anorexics. J. Pharm. Biomed. Anal. 2012, 59:38-43.
EN ISO/IEC 17025 (2005) General requirements for the competence of testing and calibration laboratories (). http://www.iso.org/.
Fienberg M. Validation of analytical methods based on accuracy profiles. J. Chromatogr. A 2007, 1158:174-183.
Feinberg M., Laurentie M. A global approach to method validation and measurement uncertainty. Accredit. Qual. Assur. 2006, 11:3-9.
De Backer B., Debrus B., Lebrun P., Theunis L., Dubois N., Decock L., Verstraete A., Hubert P., Charlier C. Innovative development and validation of an HPLC/DAD method for the qualitative and quantitative determination of major cannabinoids in cannabis plant material. J. Chromatogr. B 2009, 877:4115-4124.
De Beer J.O., De Beer T.R., Goeyens L. Assessment of quality performance parameters for straight line calibration curves related to the spread of the abscissa values around their mean. Anal. Chim. Acta 2007, 584:57-65.
De Beer J.O., Naert C., Deconinck E. The quality coefficient as performance assessment parameter of straight line calibration curves in relationship with the number of calibration points. Accredit. Qual. Assur. 2012, 17:265-274.