{"id":6151,"date":"2022-09-18T12:14:47","date_gmt":"2022-09-18T07:44:47","guid":{"rendered":"http:\/\/arasto.com\/product\/deferasirox\/"},"modified":"2023-05-08T14:18:37","modified_gmt":"2023-05-08T10:48:37","slug":"deferasirox","status":"publish","type":"product","link":"https:\/\/arasto.com\/fa\/product\/deferasirox\/","title":{"rendered":"Deferasirox"},"content":{"rendered":"

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

(BP2022)<\/p>\n

    \n
  1. Drug 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:\u00a0 Deferasirox (Brand Name: Exjade)<\/p>\n

    Compendial name: Deferasirox<\/p>\n

    Chemical name:\u00a0 4-[3,5-Bis(2-hydroxypheyl)[1,2,4]triazole-1-yl]benzoic acid;4-[3,5-Bis(2-hydroxyphenyl)-1,2,4-triazol-1-yl]benzoic acid; 4-[(3Z,5E)-3,5-bis(6-oxocyclohexa-2,4-dien-1-ylidene)-1,2,4-triazolidin-1-yl]benzoic acid.<\/p>\n

    Arasto\u2019s code:\u00a0 DES<\/p>\n

    CAS Registry Number:\u00a0 [201530-41-8]<\/p>\n

     <\/p>\n

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

      1.2. Structure (ICH 3.2.S.1.2)<\/strong><\/p>\n

      <\/p>\n

      Empirical Formula: C21H15N3O4<\/p>\n

      Molecular Weight: 373.36 g\/mol<\/p>\n

       <\/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)\u00a0<\/strong><\/p>\n

        Deferasirox is a white to off-white crystalline substance.\u00a0 It is a tri-dentate iron chelator administered orally for the treatment of iron over-load condition cause by routine blood transfusion in thalassemia major.\u00a0 It is insoluble in water but soluble at basic pH due to salt formation (> pH 9, phenoxide).\u00a0\u00a0 It is reasonably soluble in highly polar organic solvent such as DMF and DMSO and slightly soluble in alcohol. \u00a0The pKa<\/sub>\u00a0values of have been reported to be 4.57, 8.71 and 10.56 and log P 6.3 (http:\/\/www.druglead.com\/cds\/ deferasirox.html<\/a>).Deferasirox is relatively stable in \u00a0acid and base (see Stability Studies).\u00a0 \u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Reported LD50<\/sub>values for Deferasirox are: mouse oral 300 mg\/kg; rabbit oral 3200 mg\/kg; rat oral 980 mg\/kg (http:\/\/www.clearsynth.com\/docs\/MSD-CS-O-00553.pdf).<\/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, 1HNMR, 13CNMR. 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>\u00a0, IR major absorptions, 1<\/sup>HNMR d (ppm) , 13 <\/sup>CNMR \u00a0d (ppm) or HPLC retention time with values reported in the chemical literature for these compounds.<\/p>\n

        Deferasirox Impurities<\/p>\n\n\n\n\n\n\n\n\n
        Structure<\/strong><\/td>\nChemical Name<\/strong><\/td>\nBP Code<\/strong><\/td>\nArasto Code<\/strong><\/td>\n<\/tr>\n
        <\/td>\n2-hydroxy-N-(2-hydroxybenzoyl)benzamide<\/td>\nDeferasirox Impurity A<\/td>\nDeferasirox Impurity A<\/td>\n<\/tr>\n
        <\/td>\n2-(2-hydroxyphenyl)-4H-I,3-benzoxazin-4-one<\/td>\nDeferasirox Impurity B<\/td>\nDeferasirox Impurity B<\/td>\n<\/tr>\n
        <\/td>\n2-[3,S-bis(2-hydroxyphenyl)-IH-1,2,4-triazol-I-yl]benzoicacid<\/td>\nDeferasirox Impurity C<\/td>\nDeferasirox Impurity C<\/td>\n<\/tr>\n
        <\/td>\n3-[3,S-bis(2-hydroxyphenyl)-1H-I,2,4-triazol-I-yl]benzoicacid<\/td>\nDeferasirox Impurity D<\/td>\nDeferasirox Impurity D<\/td>\n<\/tr>\n
        <\/td>\nethyl 4-[3,S-bis(2-hydroxyphenyl)-IH-I,2,4-triazol-I-yl]benzoate<\/td>\nDeferasirox Impurity E<\/td>\nDeferasirox Impurity E<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n
          \n
        1. Primary and Secondary Reference Standard (ICH 3.2.S.5)<\/strong><\/li>\n<\/ol>\n

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

          Primary Reference Standard for Deferasirox is available from pharmacopoeia. We will use a secondary Primary Standard (previously referred to as Working Standard) for direct control of all batches of Deferasirox.<\/p>\n

          As per ICH (Q7, 11.1) and ICH (Q6, 2.11, 3.2, 3.3) the Secondary Primary Standard, 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 House Primary Standard of the API Deferasirox has undergone extensive characterization (UV, IR,\u00a01<\/sup>\u00a0H NMR,\u00a013<\/sup>C NMR, Mass Spec) to assure its structure, assay and purity (HPLC and\/or titration) and specification .<\/p>\n

          The Secondary Standard for Deferasirox was produced from a released batch of Deferasirox 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\n
          Product: <\/strong>Deferasirox<\/td>\nCAS No:<\/strong> 201530-41-8<\/td>\nSpec. No.: <\/strong>APC-QC-SPEC-377-00<\/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>\nWhite or slightly yellow powder.<\/td>\n<\/tr>\n
          Solubility<\/td>\nPractically insoluble in water, very soluble in dimethylsulfoxide, slightly soluble in anhydrous ethanol, practically insoluble in heptane. It shows polymorphism<\/td>\n<\/tr>\n
          Identification<\/td>\nInfrared absorption spectrophotometry<\/td>\n<\/tr>\n
          Sulfated ash<\/td>\nMax. 0.1%<\/td>\n<\/tr>\n
          Water<\/td>\nMax. 0.5%<\/td>\n<\/tr>\n
          Residual solvents<\/td>\nMethanol: Max. 3000 ppm (Class II)<\/p>\n

          Acetone: Max. 5000 ppm (Class III)<\/p>\n

          Toluene: Max. 890 ppm (Class II)<\/td>\n<\/tr>\n

          Related substances (HPLC)<\/td>\nUnidentified impurities: For each impurity, Max. 0.05%<\/p>\n

          Total: Max. 0.2%<\/td>\n<\/tr>\n

          Impurity F (HPLC)<\/td>\nMax. 0.5 ppm<\/td>\n<\/tr>\n
          Assay (HPLC)<\/td>\n98.0% to 102.0% (anhydrous 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> Store in well-closed container, protected from light and humidity.<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n","protected":false},"excerpt":{"rendered":"

          Description (BP2022) Drug Substance General Information (ICH 3.2.S.1) 1.1. Nomenclature (ICH 3.2.S.1.1) International non-proprietary name:\u00a0 Deferasirox (Brand Name: Exjade) Compendial name: Deferasirox Chemical name:\u00a0 4-[3,5-Bis(2-hydroxypheyl)[1,2,4]triazole-1-yl]benzoic acid;4-[3,5-Bis(2-hydroxyphenyl)-1,2,4-triazol-1-yl]benzoic acid; 4-[(3Z,5E)-3,5-bis(6-oxocyclohexa-2,4-dien-1-ylidene)-1,2,4-triazolidin-1-yl]benzoic acid. Arasto\u2019s code:\u00a0 DES CAS Registry Number:\u00a0 [201530-41-8]   Drug Substance General Information (ICH 3.2.S.1) 1.2. Structure (ICH 3.2.S.1.2) Empirical Formula: C21H15N3O4 Molecular Weight: 373.36 g\/mol   […]<\/p>\n","protected":false},"featured_media":7984,"comment_status":"closed","ping_status":"closed","template":"","meta":[],"product_cat":[72],"product_tag":[],"class_list":["post-6151","product","type-product","status-publish","has-post-thumbnail","hentry","product_cat-72"],"_links":{"self":[{"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/product\/6151","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=6151"}],"version-history":[{"count":1,"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/product\/6151\/revisions"}],"predecessor-version":[{"id":7986,"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/product\/6151\/revisions\/7986"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/media\/7984"}],"wp:attachment":[{"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/media?parent=6151"}],"wp:term":[{"taxonomy":"product_cat","embeddable":true,"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/product_cat?post=6151"},{"taxonomy":"product_tag","embeddable":true,"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/product_tag?post=6151"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}