{"id":6184,"date":"2022-09-18T12:52:36","date_gmt":"2022-09-18T08:22:36","guid":{"rendered":"http:\/\/arasto.com\/product\/rosuvastatin-calcium\/"},"modified":"2023-05-06T12:52:51","modified_gmt":"2023-05-06T09:22:51","slug":"rosuvastatin-calcium","status":"publish","type":"product","link":"https:\/\/arasto.com\/fa\/product\/rosuvastatin-calcium\/","title":{"rendered":"Rosuvastatin Calcium"},"content":{"rendered":"

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

(USP 44)<\/p>\n

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

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

    International non-proprietary name: Rosuvastatin Calcium (Brand Name: Crestor)<\/p>\n

    Compendial name: Rosuvastatin Calcium<\/p>\n

    Chemical name:\u00a0\u00a0\u00a0 bis[(E)-7-[4-(4-fluorophenyl)-6-isopropyl-2[methyl(methylsulfonyl) amino]pyrimidin-5-yl](3R,5S)-3,5-dihydroxyhept-6-enoic acid] calcium salt.<\/p>\n

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

    CAS Registry Number: [287714-41-4]<\/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: (\u200eC22<\/sub>H28<\/sub>FN3<\/sub>O6<\/sub>S)2<\/sub>Ca<\/p>\n

      Molecular Weight: 1001.14 g\/mol<\/p>\n

        \n
      1. Drug Substance General Information<\/strong>\u00a0(ICH 3.2.S.1 )<\/li>\n<\/ol>\n

        1.3.\u00a0 General Properties (ICH 3.2.S.1.3)<\/strong><\/p>\n

        Rosuvastatin is a white amorphous substance. It is an orally administered agent, is a member of the\u00a0drug<\/a>\u00a0class of\u00a0statins<\/a>, used in combination with exercise, diet, and weight-loss to treat\u00a0high cholesterol<\/a>\u00a0and related conditions, and to prevent\u00a0cardiovascular disease<\/a>.<\/p>\n

        Rosuvastatin is insoluble in water and some organic solvents, very slightly soluble in alcohol and somewhat soluble in DMSO, Acetone and Acetonitrile. It is soluble in water at alkaline pH due to salt formation of carboxylic acid moiety.<\/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. Each SRS has undergone extensive characterization ( IR, UV, 1HNMR, 13CNMR. Mass Spec) and determination of its purity and assay (HPLC). 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). 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 d (ppm) or HPLC retention time with values reported in the chemical literature for these compounds.<\/p>\n

        Rosuvastatin Related Compounds<\/strong><\/p>\n\n\n\n\n\n\n\n
        Structure<\/strong><\/td>\nChemical Name<\/strong><\/td>\nUSP Code<\/strong><\/td>\n<\/tr>\n
        <\/td>\nCalcium (3S,5R,E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-(N-methylmethylsulfonamido)pyrimidin-5-yl]-3,5-dihydroxyhept-6-enoate salt (1:2).<\/td>\nRosuvastatin Enantiomer<\/td>\n<\/tr>\n
        <\/td>\nCalcium (3R,5S,E)-7-{4-(4-fluorophenyl)-2-[(2-hydroxy-N,2-dimethylpropyl)sulfonamide]-6-isopropylpyrimidin-5-yl}-3,5-dihydroxyhept-6-enoate salt (1:2).<\/td>\nRosuvastatin Related Compound A<\/td>\n<\/tr>\n
        <\/td>\nCalcium (3R,5S,E)-7-(4-(4-fluorophenyl)-2-{2-[4-(4-fluorophenyl)-6-isopropyl-2-(Nmethylmethylsulfonamido)pyrimidin-5-yl]-2-hydroxy-N-methylethylsulfonamido}-6-isopropylpyrimidin-5-yl)-3,5-dihydroxyhept-6-enoate salt (1:2).<\/td>\nRosuvastatin Related Compound B<\/td>\n<\/tr>\n
        <\/td>\ntert-Butyl 2-[(4R,6S)-6-{(E)-2-[4-(4-fluorophenyl)-6-isopropyl-2-(N-methylmethylsulfonamido)pyrimidin-5-yl]vinyl}-2,2-dimethyl-1,3-dioxan-4-yl]acetate.<\/td>\nRosuvastatin Related Compound C<\/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

          5.1.\u00a0Active Pharmaceutical Ingredient<\/strong><\/p>\n

          Primary Reference Standard for Rosuvastatin calcium 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 Rosuvastatin calcium.<\/p>\n

          As per ICH (Q7, 11.1) and ICH (Q6, 2.11, 3.2, 3.3) Secondary Reference Standard, which include the API and its Related Compounds,\u00a0must 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 Rosuvastatin has undergone extensive characterization (UV, IR, 1 H NMR, 13C NMR, Mass Spec) to assure its structure, assay and purity (HPLC and\/or titration) and specification.<\/p>\n

          The Secondary Reference Standard for Rosuvastatin was produced from a released batch of Rosuvastatin 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.\u00a0It was crystallized twice more to ensure high level of purity.<\/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> Rosuvastatin calcium<\/td>\nCAS No.:<\/strong> 147098-20-2<\/td>\nSpec. No.: <\/strong>APC-QC-SPEC-392-00<\/td>\n<\/tr>\n
          Issue Date: <\/strong>Apr, 2023<\/td>\nValid up to:<\/strong> Apr, 2024<\/td>\nReference: <\/strong>USP44<\/td>\n<\/tr>\n
          Tests<\/strong><\/td>\n\n

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

          Description<\/td>\nA white to off-white, amorphous, hygroscopic powder.<\/td>\n<\/tr>\n
          Solubility<\/td>\nSoluble in dimethylformamide, in dimethylsulfoxide, in acetone and in acetonitrile; sparingly soluble in methanol; sparingly soluble to slightly soluble in water, slightly soluble in ethanol.<\/td>\n<\/tr>\n
          Identification<\/td>\nA: Infrared spectroscopy<\/p>\n

          B: Enantiomeric purity<\/p>\n

          C: Calcium test<\/td>\n<\/tr>\n

          Water determination<\/td>\nNMT 6.0%<\/td>\n<\/tr>\n
          Limit of chloride<\/td>\nNMT 0.2%<\/td>\n<\/tr>\n
          Enantiomeric Purity (HPLC)<\/td>\nNMT 0.15%<\/td>\n<\/tr>\n
          Residual Solvents<\/td>\nAcetone: Max. 5000 ppm (Class III)<\/p>\n

          Isopropanol: Max. 5000ppm (class III)<\/p>\n

          Ethyl acetate: Max. 5000ppm (class\u0428)<\/td>\n<\/tr>\n

          Organic impurities (HPLC)<\/td>\nRosuvastatin related compound A: NMT 0.2%<\/p>\n

          Rosuvastatin diastereomers: NMT 0.5%<\/p>\n

          Rosuvastatin ketone: NMT 0.8%<\/p>\n

          Rosuvastatin lactone: NMT 0.15%<\/p>\n

          Rosuvastatin dehydroanalog: NMT 0.15%<\/p>\n

          Any unspecified impurity: NMT 0.10%<\/p>\n

          Total impurities: NMT 1.5%<\/td>\n<\/tr>\n

          Assay (HPLC)<\/td>\n97.0% to 103.0% (on the anhydrous and solvent-free basis)<\/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> Preserve in well-closed containers, protected from light. Store at controlled room temperature.<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n","protected":false},"excerpt":{"rendered":"

          Description (USP 44) Drug Substance General Information (ICH 3.2.S.1 ) 1.1. Name (ICH 3.2.S.1.1) International non-proprietary name: Rosuvastatin Calcium (Brand Name: Crestor) Compendial name: Rosuvastatin Calcium Chemical name:\u00a0\u00a0\u00a0 bis[(E)-7-[4-(4-fluorophenyl)-6-isopropyl-2[methyl(methylsulfonyl) amino]pyrimidin-5-yl](3R,5S)-3,5-dihydroxyhept-6-enoic acid] calcium salt. Arasto\u2019s code: ROS CAS Registry Number: [287714-41-4] Drug Substance General Information (ICH 3.2.S.1) 1.2. Structure (ICH 3.2.S.1.2) Empirical formula: (\u200eC22H28FN3O6S)2Ca Molecular Weight: […]<\/p>\n","protected":false},"featured_media":7145,"comment_status":"closed","ping_status":"closed","template":"","meta":[],"product_cat":[72],"product_tag":[],"class_list":["post-6184","product","type-product","status-publish","has-post-thumbnail","hentry","product_cat-72"],"_links":{"self":[{"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/product\/6184","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=6184"}],"version-history":[{"count":2,"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/product\/6184\/revisions"}],"predecessor-version":[{"id":7149,"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/product\/6184\/revisions\/7149"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/media\/7145"}],"wp:attachment":[{"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/media?parent=6184"}],"wp:term":[{"taxonomy":"product_cat","embeddable":true,"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/product_cat?post=6184"},{"taxonomy":"product_tag","embeddable":true,"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/product_tag?post=6184"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}