{"id":6132,"date":"2022-09-18T12:24:14","date_gmt":"2022-09-18T07:54:14","guid":{"rendered":"http:\/\/arasto.com\/product\/montelukast-sodium\/"},"modified":"2023-05-06T12:49:19","modified_gmt":"2023-05-06T09:19:19","slug":"montelukast-sodium","status":"publish","type":"product","link":"https:\/\/arasto.com\/fa\/product\/montelukast-sodium\/","title":{"rendered":"Montelukast Sodium"},"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. Nomenclature (ICH 3.2.S.1.1)<\/strong><\/p>\n

    International non-proprietary name:\u00a0 Montelukast Sodium (Brand Name: Singulair)<\/p>\n

    Compendial name:\u00a0 Montelukast Sodium<\/p>\n

    Chemical name:\u00a0 [R<\/em>-(E<\/em>)]-1-[[[1-[3-[2-(7-chloro-2-quinolinyl)ethenyl]phenyl]-3-[2-(hydroxymethylethyl)phenyl]propyl]thio]methyl]-cyclopropane acetic acid, monosodium salt.<\/p>\n

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

    CAS Registry Number: CAS [151767-02-1]<\/p>\n

      \n
    1. \u00a0Drug 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: C35<\/sub>H35<\/sub>ClNNaO3<\/sub>S<\/p>\n

      Molecular Weight: 608.18 g\/mol<\/p>\n

      \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

        Montelukast Sodium is a white to off-white powder.\u00a0 It is administered orally for\u00a0prophylaxis<\/a>\u00a0and chronic treatment of\u00a0asthma<\/a>, exercise-induced bronchoconstriction, and allergic rhinitis.\u00a0 It is soluble in water and most organic solvents except saturated hydrocarbons.\u00a0 Estimated pKa<\/sub>\u00a0of montelukast is 4.3 (http:\/\/toxnet.nlm.nih.gov\/cgi-bin\/sis\/search\/a?dbs+hsdb:@term+@DOCNO<\/a>\u00a0+7582) and its calculated log P has been reported to be 8.98 (http:\/\/www.ncbi.nlm.nih. gov\/pmc\/articles\/PMC2641037\/).\u00a0 Montelukast sodium is unstable in acid and base and undergoes oxidation at the sulfur tom to afford a sulfoxide impurity.\u00a0 It can also undergo light-induced double bond isomerization (see Stability Studies).\u00a0 Oral LD50<\/sub>\u00a0for Montelukast Sodium in rat has been reported to be>5000 mg\/kg (http:\/\/www.lclabs.com\/MSDS\/M-4966MSDS.php4).<\/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\n\n\n\n\n\n
        Structure<\/strong><\/td>\nChemical Name<\/strong><\/td>\nUSP Code<\/strong><\/td>\n<\/tr>\n
        <\/td>\nDicyclohexylammonium (RS,E)-2-(1-{[(1-{3-[2-(7-chloroquinolin-2-yl)vinyl]phenyl}-3-[2-(2-hydroxypropan-2- yl)phenyl]propyl)thio]methyl}cyclopropyl)acetate<\/td>\nMonelukast Racemate<\/td>\n<\/tr>\n
        <\/td>\nDicyclohexylammonium (R,E)-2-(1-{[(1-{3-[2-(7-chloroquinolin-2-yl)vinyl]phenyl}-3-[2-(2- hydroxypropan-2-yl)phenyl]propyl)thio]methyl}cyclopropyl)acetate<\/td>\nMontelukast Dicyclohexylamine<\/td>\n<\/tr>\n
        <\/td>\nMontelukast containing sulfoxide impurity, michael adducts 1 and 2, methylketone impurity, and methylstyrene impurity<\/td>\nMontelukast for Peak Identification<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

        Montelukast sodium Related Compounds<\/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 montelukast sodium is available from USP. We will use a Secondary Reference Standard (previously referred to as Working Standard) for direct control of all batches of montelukast sodium.<\/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,\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 Secondary Reference Standards of the API montelukast sodium 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 \/max<\/sub>\u00a0with USP Primary Reference Standard.<\/p>\n

          The Secondary Reference Standard for montelukast sodium was produced from a released batch of montelukast sodium 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>Montelukast Sodium<\/td>\nCAS No.: <\/strong>151767-02-1<\/td>\nSpec. No.: <\/strong>APC-QC-SPEC-385-00<\/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>\nWhite or almost white, hygroscopic powder.<\/td>\n<\/tr>\n
          Solubility<\/td>\nFreely soluble to very soluble in alcohol; freely soluble in water and in methylene chloride.<\/td>\n<\/tr>\n
          Identification<\/td>\nA: Infrared Spectroscopy<\/p>\n

          B: Sodium Test<\/p>\n

          C: Enantiomeric purity<\/td>\n<\/tr>\n

          Water Determination<\/td>\nNMT 4.0%<\/td>\n<\/tr>\n
          Enantiomeric Purity<\/td>\nNMT 0.2% of The S-enantiomer<\/td>\n<\/tr>\n
          Residual Solvents<\/td>\nN-heptane: NMT 5000 ppm (Class \u0428)<\/p>\n

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

          Organic Impurities (HPLC)<\/td>\nSulfoxide impurity: NMT 0.2%<\/p>\n

          Cis-isomer: NMT 0.15%<\/p>\n

          Michael Adducts 1c<\/sup>and 2d<\/sup> : NMT 0.15%<\/p>\n

          Methylketone impurity: NMT 0.15%<\/p>\n

          Methylstyrene impurity: NMT 0.3 %<\/p>\n

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

          Total impurities: NMT 0.6 %<\/td>\n<\/tr>\n

          Assay (HPLC)<\/td>\n98.0% to 102.0 % (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 tight containers, protected from light. Store at 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. Nomenclature (ICH 3.2.S.1.1) International non-proprietary name:\u00a0 Montelukast Sodium (Brand Name: Singulair) Compendial name:\u00a0 Montelukast Sodium Chemical name:\u00a0 [R-(E)]-1-[[[1-[3-[2-(7-chloro-2-quinolinyl)ethenyl]phenyl]-3-[2-(hydroxymethylethyl)phenyl]propyl]thio]methyl]-cyclopropane acetic acid, monosodium salt. Arasto\u2019s code:\u00a0 MON CAS Registry Number: CAS [151767-02-1] \u00a0Drug Substance General Information (ICH 3.2.S.1) 1.2. Structure (ICH 3.2.S.1.2) Empirical formula: C35H35ClNNaO3S Molecular Weight: […]<\/p>\n","protected":false},"featured_media":7141,"comment_status":"closed","ping_status":"closed","template":"","meta":[],"product_cat":[72],"product_tag":[],"class_list":["post-6132","product","type-product","status-publish","has-post-thumbnail","hentry","product_cat-72"],"_links":{"self":[{"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/product\/6132","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=6132"}],"version-history":[{"count":1,"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/product\/6132\/revisions"}],"predecessor-version":[{"id":7143,"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/product\/6132\/revisions\/7143"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/media\/7141"}],"wp:attachment":[{"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/media?parent=6132"}],"wp:term":[{"taxonomy":"product_cat","embeddable":true,"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/product_cat?post=6132"},{"taxonomy":"product_tag","embeddable":true,"href":"https:\/\/arasto.com\/fa\/wp-json\/wp\/v2\/product_tag?post=6132"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}