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 nitrogen gas as the mobile phase. Our method is also compatible with the GC-MS (gas chromatography-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 include 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).
Highlights
Benzene is known to cause central nervous system depression in addition to destroying bone marrow, which in turn leads to damage to the hematopoietic system
The evidence reported to date, indicates that 1,2-dichloroethane is potentially genotoxic, and excess cancer risk of 10−5 was reported at exposures of 0.05 mg/d for 50 kg human based on hemangiosarcoma using a linearized multistage model without body surface correction
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Summary
Benzene (fig. 1) is known to cause central nervous system depression in addition to destroying bone marrow, which in turn leads to damage to the hematopoietic system. Benzene has been demonstrated to be a human carcinogen (i.e., lymphatic and hematopoietic cancers), while in animal studies, Zymbal gland tumors, preputial gland tumors, skin carcinomas, mammary gland tumors, and leukemia have been reported. From the data of human leukemia and benzene exposure correlations, a daily intake of 0.02 mg was found to be associated with a lifetime excess cancer risk of 10−5 (IRIS), and we note that the guideline value for benzene is 0.02 mg/d (2 ppm) [1−5]. The evidence reported to date, indicates that 1,2-dichloroethane is potentially genotoxic, and excess cancer risk of 10−5 was reported at exposures of 0.05 mg/d for 50 kg human based on hemangiosarcoma using a linearized multistage model without body surface correction. The guideline value for 1,2-dichloroethane is 0.05 mg/d (5 ppm) [1−5]
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