A kind of detection method of azobisisobutylamidine dihydrochloride

Abstract

The invention belongs to the field of detection of drug residues, and in particular relates to a detection method for azobisisobutylamidine dihydrochloride, which comprises using HPLC to detect azobisisobutylamidine dihydrochloride; using preparation solution C to prepare a reference substance and Need testing solution; said preparation C is prepared by mixing salt chloride and water, wherein the concentration of salt chloride is 10-40mmol / L. This method solves the problem of poor stability of low-concentration V-50 solutions, and obtains the technical effect of detecting V-50 with good repeatability. At the same time, the method can be quantified to a limit of not less than 0.01 μg / ml, which meets the requirements of relevant regulations. The impurity quantification and The requirement of method validation is of far-reaching significance for the accurate determination of trace V-50 impurity residues in medicines and ensuring the safety of medicines.

Description

technical field [0001] The invention belongs to the field of detection of drug residues, and in particular relates to a detection method of azobisisobutylamidine dihydrochloride. Background technique [0002] Azobisisobutylamidine dihydrochloride, referred to as V-50, is a water-soluble azo initiator, which is widely used in aqueous solution polymerization and emulsion polymerization of polymer synthesis. Many manufacturers of polymer pharmaceutical synthesis have realized that It has excellent performance and has been applied on a large scale. [0003] V-50 chemical structural formula: [0004] [0005] Chinese chemical name: 2,2'-azobisisobutylamidine dihydrochloride [0006] Molecular formula: C 8 h 18 N 6 2HCl [0007] Chemical Abstracts (CAS) No.: 2997-92-4 [0008] V-50 is the initiator in the polymerization step of the macromolecular drug production process. According to the polymerization reaction mechanism: V-50 generates two cationic radicals through homo...

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Problems solved by technology

[0010] There are multiple ultraviolet absorbing groups in the V-50 structure, which has strong ultraviolet absorption. In the prior art, the detection of V-50 adopts ultraviolet-visible spectrophotometry (UV-Vis) or high-performance liquid chromatography (HPLC) technology , the solvent is pure water, and the concentration of V-50 is only at the microgram level, that is, each milliliter of the solution contains several to tens of micrograms of V-50. According to the requirements of the control limit of genotoxic impurities in the above-mentioned ICH M7, the microgram level of V-50 The concentration can not meet the inspection requirements, and the V-50 needs to be diluted to 0.1 μg / ml when testing this product; however, we found in the course of our research that as the concentration decreases, the stability of the V-50 solution becomes worse. When the V-50 solution is diluted to When the concentration is 0.1 μg / ml, continuous injection of 6 needles, the RSD of V-50 peak area exceeds 30%, and the change of V-50 peak area exceeds 80% within 8 hours, which does not meet the requirements of the Chinese Pharmacopoeia 2015 edition "9101 Drug Quality Standard Analysis Method Validation" Acceptable ranges for method validation as specified in the Guiding Principles

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