{"id":6147,"date":"2022-09-18T12:11:54","date_gmt":"2022-09-18T07:41:54","guid":{"rendered":"http:\/\/arasto.com\/product\/azathioprine\/"},"modified":"2023-05-06T12:26:40","modified_gmt":"2023-05-06T08:56:40","slug":"azathioprine","status":"publish","type":"product","link":"https:\/\/arasto.com\/fa\/product\/azathioprine\/","title":{"rendered":"Azathioprine"},"content":{"rendered":"

Description<\/strong><\/p>\n

(USP 44\/BP 2022)<\/p>\n

    \n
  1. \u00a0Drug Substance General Information (ICH 3.2.S.1)<\/strong><\/li>\n<\/ol>\n

    1.1. Nomenclature (ICH 3.2.S.1.1)<\/strong><\/p>\n

    International non-proprietary name: Azathioprine (Brand Name: Azasan, CellCept, Simulect, Imuran, Rapamune)<\/p>\n

    Compendial name:\u00a0\u00a0\u00a0 Azathioprine<\/p>\n

    Chemical name: 6-(1-methyl-4-nitro-1H-imidazol-5-yl) thio] 1H-purine-6-[(1-methyl-4-nitro-5-imidazolyl-5yl) mercaptopurine<\/p>\n

    Arasto\u2019s code: AZA<\/p>\n

    CAS Registry Number: [446-86-6]<\/p>\n

    <\/p>\n

    Empirical formula: C9<\/sub>H7<\/sub>N7<\/sub>O2<\/sub>S<\/p>\n

    Molecular Weight: 277.26<\/p>\n

      \n
    1. Drug Substance General Information (ICH 3.2.S.1)<\/strong><\/li>\n<\/ol>\n

      1.3. General Properties (ICH 3.2.S.1.3)<\/strong><\/p>\n

      Azathioprine is a light yellow to light greenish-yellow crystalline compound.\u00a0 It is orally administered for the treatment of renal homotransplantation and rheumatoid arthritis.\u00a0 Azathioprine is insoluble in water or organic solvents (except hot DMSO).\u00a0 Azathioprine pKa<\/sub>\u00a0has been reported as 8.07 at 25\u00a0o<\/sup>C (Am. J. Ana. Chem<\/em>.\u00a02011<\/strong>,\u00a01<\/em>, 14-24).\u00a0\u00a0\u00a0 The addition of one molar equivalent of alkali affords Azathioprine salt which is water soluble. The salt of Azathioprine is sufficiently soluble to make a 10 mg\/ml water solution which is stable for 24 hours at 15\u00b0 to 25\u00b0C. Azathioprine is stable in solution at neutral or acid pH but hydrolysis to\u00a0mercaptopurine<\/a>\u00a0occurs in excess sodium hydroxide (0.1N), especially on warming. Conversion to mercaptopurine also occurs in the presence of sulfhydryl compounds such as\u00a0cysteine<\/a>, glutathione, and hydrogen sulfide. LD50<\/sub>has been reported to be 535 mg\/kg Oral in rat (oral)\u00a0http:\/\/msds.chem.ox.ac.uk<\/a>\u00a0\/AZ\/ Azathioprine.html.<\/p>\n

      The determination of purity and assay of APIs require comparison of the product with their respective Reference Standards (RS) and Related Compounds (RC or known impurities).\u00a0 Accordingly, ICH regulations on the purity and assay of reference standard and related compounds are clearly defined and must be followed by drug substance and drug product manufacturers.<\/p>\n

      According to ICH Q7, 11.1 there are 3 types of standards.\u00a0 This is summarized in the following chart and discussed in detail below.<\/p>\n

      <\/p>\n

      The impurities provided in the following table represent Secondary Reference Standards (SRS) that are prepared in-house by synthesis or by isolation.\u00a0 Each SRS has undergone extensive characterization (IR, UV, 1<\/sup>HNMR, 13<\/sup>CNMR. Mass Spec) and determination of its purity and assay (HPLC).\u00a0 For specification of the SRS of those products that have a monograph, the SRS is compared with a pharmacopoeia Primary Reference Standard (UV, HPLC retention time).\u00a0 For specification of those products that do not have a monograph (known as House Primary Standard), we compare their UV \u03b5 or \u05d2\/max<\/sub>, IR major absorptions, 1<\/sup>HNMR d(ppm), 13<\/sup>CNMR d(ppm) or HPLC retention time with values reported in the chemical literature for these compounds.<\/p>\n

      <\/strong><\/p>\n

        \n
      1. Primary and Secondary Reference Standard (ICH 3.2.S.5)<\/strong><\/li>\n<\/ol>\n

        \u00a05.1.\u00a0Active Pharmaceutical Ingredient<\/strong><\/p>\n

        Primary Reference Standard for Azathioprine is available from United States Pharmacopoeia. We will use a Secondary Reference Standard (previously referred to as Working Standard) for direct control of all batches of azathioprine.<\/p>\n

        As per ICH (Q7, 11.1) and ICH (Q6, 2.11, 3.2, 3.3) the Secondary Reference Standards, which include the API and its Related Compounds, must be examined for their proof of structure (characterization), assay and purity and specification (identification by comparison). Furthermore, ICH Guideline on the Preparation of Common Technical Document (Q4M) requires that the data obtained from characterization, assay and purity and specification must be included in section 3.2.S.3.2 for Related Compounds (already discussed in that section) and section 3.2.S.5 of the DMF for the API.\u00a0To this end, the Secondary Reference Standards of the API azathioprine has undergone extensive characterization (UV, IR,\u00a01<\/sup>\u00a0H NMR,\u00a013<\/sup>C NMR, and Mass Spec) to assure its structure, assay and purity (HPLC and\/or titration) and specification (comparison of its HPLC retention time and UV \u05d2<\/sub>\/max<\/sub>\u00a0with USP Primary Reference Standard.<\/p>\n

        The Secondary Reference Standard for azathioprine was produced from a released batch of azathioprine by subjecting it to an additional crystallization from the final solvent system used in the production of the API to avoid the possibility of other polymorph formation.<\/p>\n

        SPECIFICATION OF ANALYSIS<\/h1>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
        Product: <\/strong>Azathioprine<\/td>\nCAS No.: <\/strong>446-86-6<\/td>\nSpec. No.: <\/strong>APC-QC-SPEC-371-00<\/td>\n<\/tr>\n
        Issue Date: <\/strong>Apr, 2023<\/td>\nValid up to:<\/strong> Apr, 2024<\/td>\nReference: <\/strong>BP2022<\/td>\n<\/tr>\n
        Tests<\/strong><\/td>\n\n

        Specifications<\/h2>\n<\/td>\n<\/tr>\n

        Appearance<\/td>\nPale-yellow powder.<\/td>\n<\/tr>\n
        Solubility<\/td>\nPractically insoluble in water and in ethanol (96%). It is soluble in dilute solutions of alkali hydroxides and sparingly soluble in dilute mineral acids.<\/td>\n<\/tr>\n
        Identification<\/td>\nInfrared absorption spectrophotometry<\/td>\n<\/tr>\n
        Loss on drying<\/td>\nMax. 1.0%<\/td>\n<\/tr>\n
        Sulphated Ash<\/td>\nMax. 0.1%<\/td>\n<\/tr>\n
        Residual Solvents<\/td>\nMethanol: Max. 3000 ppm (Class II)<\/td>\n<\/tr>\n
        Related substances (HPLC)<\/td>\nImpurity A: Max. 0.15%<\/p>\n

        Impurity B: Max. 0.15%<\/p>\n

        Unspecified impurities: Max. 0.10%<\/p>\n

        Total impurities: Max. 0.5%<\/td>\n<\/tr>\n

        Assay<\/td>\n98.5% to 101.0% (dried substance)<\/td>\n<\/tr>\n
        Prepared by:<\/strong> M. Shahbazi, B.Sc.Chem.<\/td>\nChecked by:<\/strong> A. Forghani, B.Sc.Chem.<\/td>\n<\/tr>\n
        Approved by:<\/strong> F. Javadizadeh, M.Sc.Chem.<\/td>\n<\/tr>\n
        Storage:<\/strong> Protected from light.<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

        \n","protected":false},"excerpt":{"rendered":"

        Description (USP 44\/BP 2022) \u00a0Drug Substance General Information (ICH 3.2.S.1) 1.1. Nomenclature (ICH 3.2.S.1.1) International non-proprietary name: Azathioprine (Brand Name: Azasan, CellCept, Simulect, Imuran, Rapamune) Compendial name:\u00a0\u00a0\u00a0 Azathioprine Chemical name: 6-(1-methyl-4-nitro-1H-imidazol-5-yl) thio] 1H-purine-6-[(1-methyl-4-nitro-5-imidazolyl-5yl) mercaptopurine Arasto\u2019s code: AZA CAS Registry Number: [446-86-6] Empirical formula: C9H7N7O2S Molecular Weight: 277.26 Drug Substance General Information (ICH 3.2.S.1) 1.3. General […]<\/p>\n","protected":false},"featured_media":7108,"comment_status":"closed","ping_status":"closed","template":"","meta":[],"product_cat":[79],"product_tag":[],"class_list":["post-6147","product","type-product","status-publish","has-post-thumbnail","hentry","product_cat-hazard-api-fa"],"_links":{"self":[{"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/product\/6147","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/product"}],"about":[{"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/types\/product"}],"replies":[{"embeddable":true,"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/comments?post=6147"}],"version-history":[{"count":2,"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/product\/6147\/revisions"}],"predecessor-version":[{"id":7110,"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/product\/6147\/revisions\/7110"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/media\/7108"}],"wp:attachment":[{"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/media?parent=6147"}],"wp:term":[{"taxonomy":"product_cat","embeddable":true,"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/product_cat?post=6147"},{"taxonomy":"product_tag","embeddable":true,"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/product_tag?post=6147"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}