This content is current only at the time of printing. This document was printed on 4 August 2020. A current copy is located at https://apvma.gov.au/node/2770
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Standard for quintozene active constituent
the material shall consist of quintozene together with related manufacturing impurities and shall be an off-white powder, free from visible extraneous matter and added modifying agents.
6.1 Active constituent: 950 g/kg minimum
6.2 Toxicologically Significant Impurities:
Hexachlorobenzene (CASRN: 118-74-1): 350 mg/kg maximum
Pentachlorobenzene (CASRN: 608-93-5): 0.3 mg/kg maximum
Total polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) calculated as the sum of the toxic equivalents (TEQs) of the 17 toxicologically significant PCDD and PCDF congeners, using the WHO (2005) toxic equivalence factors (TEFs)1: 0.005 mg/kg (5 ppb) maximum
1 TEFs as defined by Van den Berg et al. (2006) Toxicol. Sci., 93 (2): 223-241.
Analytical method for determination of PCDDs and PCDFs
With regard to the analysis of PCDDs and PCDFs, results must be generated by an analytical laboratory capable of determining PCDDs and PCDFs using a suitable method such as US EPA Method 1613, Revision B: Tetra – through Octa – Chlorinated Dioxins and Furans by Isotope Dilution HRGC/HRMS, or SW-846 Test Method 8290A: Polychlorinated Dibenzo-p-dioxins (PCDDs) and Polychlorinated Dibenzofurans (PCDFs) by High-Resolution Gas Chromatography/High Resolution Mass Spectrometry (HRGC/HRMS). The United Nations Environment Program (UNEP) maintains a database of laboratories conducting analyses of persistent organic pollutants, including PCDDs and PCDFs1.
When providing results for PCDDs and PCDFs, please include details of the method, or where a published method such as 1613B is used, details of any deviations from that method, and full validation data including linearity, precision, accuracy, method detection limits, and reporting/quantitation limits for each of the 17 congeners of interest, plus examples of all calculations undertaken in the interpretation of the raw data.
1UNEP databank of laboratories analysing POPs , see: http://chm.pops.int/Implementation/GlobalMonitorin...
- The analytical method used for the determination of the active constituent and toxicological significant impurities must be validated in accordance with the APVMA guidelines for the validation of analytical methods.
- The APVMA guidelines on validation of analytical methods state that 'Analytical methods described in CIPAC handbooks and AOAC International Manual, and in recognized pharmacopoeias [BP, BP (Vet), Ph Eur and USP] for a particular active constituent or formulation are regarded as validated and do not require revalidation'. However, the suitability of these methods must be verified under actual conditions of use ie, the selectivity and accuracy of the method should be demonstrated for the published method when applied to the relevant sample matrix and laboratory conditions.
- When a CIPAC or AOAC method is used for the assay of an active constituent in a bulk active constituent, there is no matrix. The registrants need to check the specificity of the method to ensure there is no interference from impurities or degradation products. However, determination of accuracy of the method is not required as there is no potential for the product matrix to have an effect on the determination of the active constituent. However, when a CIPAC or AOAC method is used for the assay of an active constituent in a formulated product, determination of both specificity and accuracy is required as the matrix is relevant in formulated products (formulated products have different composition and quantities of excipients).
- Unless the scope of the collaborative method (CIPAC and AOAC) also includes toxicologically significant impurities in the active constituent, validation data for impurities are required.