Method for detecting azobis(isobutylamidine hydrochloride)

Abstract

The invention belongs to the medical drug residue detection field and especially relates to a method for detecting azobis(isobutylamidine hydrochloride). The method comprises the following steps of using HPLC to detection the azobis(isobutylamidine hydrochloride); and using a preparation liquid C to prepare a reference substance and a test solution, wherein the preparation liquid C is prepared through mixing chloride and water, and the concentration of the chloride is 10 to 40 mmol / L. By using the method, a problem of poor stability of a low concentration V-50 solution is solved, and a technical effect of V-50 detection with good repeatability is obtained. And simultaneously, in the method, an amount can be quantified to a limit which is not less than 0.01 mug / ml, and the method satisfiesimpurity quantification of a relevant regulation and a methodological verification requirement and has profound significance for accurately determining trace V-50 impurity residues in drugs and ensuring the safety of the drug.

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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