SIMULTANEOUS TRACE LEVEL DETERMINATION OF BENZENE AND 1,2-DICHLOROETHANE BY GC-HS / GC-MS IN SEVERAL PHARMACEUTICAL DRUG SUBSTANCES


Sayeeda Sultana, Balaji Nagarajan

Abstract


Objective: We herein report the simultaneous trace level determination of benzene and 1,2-dichloroethane in several active pharmaceutical substances by GC-HS (gas chromatograph-head space) using a DB-624 column.

 

Methods: This GC-HS method was developed based on an oven-programmed approach using a nitrogen gas as the mobile phase. Our method is also compatible with the GC-MS (gas chromatograph-mass spectrometry) technique using helium as the mobile phase instead of nitrogen. The successful separation of benzene and 1,2-dichloroethane was established by confirmation of their corresponding specific molecular masses.

 

Results: The retention time of benzene and 1,2-dichloroethane were found to be 34.8 min and 35.6 min, respectively. The linearity was found in the range of concentration of 0.63-4.22 ppm and 1.49-9.96 ppm for benzene and 1,2-dichloroethane. The detection limit and quantification limit for benzene were 0.2 and 0.6 ppm, while those of 1,2-dichloroethane were 0.6 ppm and 1.5 ppm. These values were calculated using our developed method with respect to the test concentration of 500 mg/ml. The recovery of benzene and 1,2-dichloroethane were found to be 89–110% and 91–105%, respectively for the various pharmaceutical drug substances. The specificity of the method was studied using 20 solvents which includes benzene and 1,2-dichloroethane.

 

Conclusion: We expect that our method will be applicable for the simultaneous trace level determination of benzene and 1,2-dichloroethane during the control of manufacturing processes, and for use in rapid analysis for quality control in the pharmaceutical industry. Finally, this method was validated according to the International Conference on Harmonization (ICH) Validation Guidelines Q2 (R1).


Keywords


GC, GC-MS DB-624, benzene, 1,2-dichloroethane, class-1 solvent, pharmaceutical substance

References


https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM073397.pdf

International Conference on Harmonisation (ICH) of Technical Requirements for the Registration of Pharmaceuticals for Human Use, Q3C (R6): Impurities: Guidelines for Residual Solvents, Step 4, 2016.

United States Pharmacopoeia 40, United States Pharmacopeial Convention, Inc., Rockville, MD, USA, 2017.

European Pharmacopoeia, 9.0, Council of Europe, Strasbourg, France, 2017.

Japanese Pharmacopoeia, 17th ed., Society of Japanese Pharmacopoeia, Tokyo, 2017.

Balaji N, Sultana S. Reversed-phase UHPLC enantiomeric separation of rasagiline salts using a Chiralpak® AGP column. Sci Pharm 2017;85:1–13.

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.

Autry WD, 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;34:1299–308.

Balaji N, Sultana S. Trace level determination and quantification of potential genotoxic impurities in dasatinib drug substance by UHPLC/INFINITY LC. Int J Pharm Pharm Sci 2016;8:209–16.

Autry WD, 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;55:1017–23.

Autry WD, 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;18:4034–8.

Weiss AM. Buying prescription drugs on the Internet: promises and pitfalls, Cleve Clin J Med 2006;73:282–8.

Veronin M, Youan BB, Magic bullet gone astray: Medications and the Internet. Science 2004;305:481.

Balaji N, Sultana S. Ultra-high performance liquid chromatographic determination of genotoxic impurities in febuxostat drug substance and products. Asian J Pharm Clin Res 2017;10:324–30.

European Alliance For Access to Safe Medicines: 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.

Balaji N, Sultana S. GC and GC-MS detection of alkyl mesylates in active pharmaceutical ingredients. Int J Pharm Sci Rev Res 2017;46:88–92.

Sacre PY, Deconinck E, Chiap P, Crommen J, Rozet E, Courselle P, De Beer JO. 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;1218:6439–47.

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 (www.iso.org).

Balaji N, Sultana S. LC determination of diastereomeric impurities of entecavir in drug substances and drug products. Res J Pharm Biol Chem Sci 2016;7:1848–59.

Fienberg M. Validation of analytical methods based on accuracy profiles. J Chromatogr A 2007;1158:174–83.

M Feinberg, M Laurentie, 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;877:4115–24.

Balaji N, Sultana S. Sensitive determination of related substances in pioglitazone hydrochloride by HPLC. Int J Appl Pharm 2017;9:34–41.

De Beer JO, De Beer TR, 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 JO, 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;17:265–74.

International Conference on Harmonisation (ICH) of Technical Requirements for the Registration of Pharmaceuticals for Human Use, Q2 (R1): Impurities: Guidelines for Residual Solvents, Step 4, 2005.




Fatal error: Call to a member function getGalleyLabel() on null in /home/innowar1/public_html/journals/cache/t_compile/%%38^38D^38D7420B%%article.tpl.php on line 182