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    Certificate of Analysis: Ranitidine Hydrochloride

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    Bagus dwi setiawan
    This certificate of analysis provides information on a certified reference material of ranitidine hydrochloride. It summarizes the results of tests to determine purity, identity, and homogeneity. The material has a certified purity of 99.4% based on mass balance/impurity determination. Tests such as HPLC, FTIR, NMR, and elemental analysis confirm the identity and structure match pharmacopeial reference standards. Homogeneity was also confirmed through statistical analysis of samples.

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    Certificate of Analysis: Ranitidine Hydrochloride

    Uploaded by

    Bagus dwi setiawan
    107 views8 pages
    This certificate of analysis provides information on a certified reference material of ranitidine hydrochloride. It summarizes the results of tests to determine purity, identity, and homogeneity. The material has a certified purity of 99.4% based on mass balance/impurity determination. Tests such as HPLC, FTIR, NMR, and elemental analysis confirm the identity and structure match pharmacopeial reference standards. Homogeneity was also confirmed through statistical analysis of samples.

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    Coa Ranitidin Hcl

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    This certificate of analysis provides information on a certified reference material of ranitidine hydrochloride. It summarizes the results of tests to determine purity, identity, and homogeneity. The material has a certified purity of 99.4% based on mass balance/impurity determination. Tests such as HPLC, FTIR, NMR, and elemental analysis confirm the identity and structure match pharmacopeial reference standards. Homogeneity was also confirmed through statistical analysis of samples.

    Copyright:

    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd
    Download as pdf or txt
    107 views8 pages

    Certificate of Analysis: Ranitidine Hydrochloride

    Uploaded by

    Bagus dwi setiawan
    This certificate of analysis provides information on a certified reference material of ranitidine hydrochloride. It summarizes the results of tests to determine purity, identity, and homogeneity. The material has a certified purity of 99.4% based on mass balance/impurity determination. Tests such as HPLC, FTIR, NMR, and elemental analysis confirm the identity and structure match pharmacopeial reference standards. Homogeneity was also confirmed through statistical analysis of samples.

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    © All Rights Reserved
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    of 8

    Certificate of Analysis

    ISO GUIDE 34
    ACLASS Cert# AR-1470

    ISO/IEC 17025
    RANITIDINE HYDROCHLORIDE
    ACLASS Cert# AT-1467 CERTIFIED REFERENCE MATERIAL
    H3C
    NH HCl CH3

    S N
    N CH3
    H O
    +
    N
    O O-

    CERTIFIED PURITY: 99.4%, Ucrm = ±0.1% k = 2


    (Mass Balance/ basis)

    NOMINAL PACKAGE SIZE: 500mg

    CATALOG #: PHR1026 LOT #: LRAA5630

    CERTIFICATE VERSION: LRAA5630.1 ISSUE DATE: 07 July 2014


    Note: Certificates may be updated due to Pharmacopeial Lot changes or the availability of new data.
    Check our website at: www.sigma-aldrich.com for the most current version.

    CRM EXPIRATION: 31 December 2019 (Proper Storage and Handling Required).

    RECEIPT DATE: ________________


    Note: this space is provided for convenience only and its use is not required.

    STORAGE: Store at Room Temperature/Protect from Light, keep container tightly


    closed. Attachment of a 20 mm aluminum crimp seal recommended for unused portions.

    CHEMICAL FORMULA: C13H22N4O3S·HCl MW: 350.86

    PHYSICAL DESCRIPTION: White powder in amber vial CAS #: 66357-59-3

    HAZARDS: Read Safety Data Sheet before using. All chemical reference materials
    should be considered potentially hazardous and should be used only by qualified
    laboratory personnel.

    Page 1 of 8
    INSTRUCTIONS FOR USE: Do not dry, use as is. The internal pressure of the container
    may be slightly different from the atmospheric pressure at the user’s location. Open
    slowly and carefully to avoid dispersion of the material. This material is intended for
    R&D use only. Not for drug, household or other uses.

    TRACEABILITY ASSAY
    Comparative assay demonstrates direct traceability to Pharmacopeial Standards
    Specification: 97.5% to 102.0% (USP)

    ASSAY vs. USP REFERENCE STANDARD (as is basis)


    ASSAY VALUE vs. USP LOT
    99.6% H1G103
    Labeled Content = 0.997mg/mg

    ASSAY vs. BP CRS (as is basis)


    ASSAY VALUE vs. BP BATCH
    99.98% (as HCl) 2984
    89.6% (as free base) Labeled Content = 89.4% as free base

    METHOD: HPLC (ref.: Ranitidine Hydrochloride USP33)


    Column: Wakosil 5C18RS 4.6 x 150 mm, 5um
    Mobile Phase: Solution A: Phosphate buffer, acetonitrile (98:2)
    Solution B: Phosphate buffer, acetonitrile (78:22)
    Phosphate buffer: Water, phosphoric acid, NaOH, pH 7.1
    Gradient:
    Time(minutes) Solution A % Solution B % Elution
    0 - 10 100 → 0 0 → 100 Linear gradient
    10 - 15 0 100 Isocratic
    15 - 16 0 → 100 100 → 0 Linear gradient
    16 - 20 100 0 Re-equilibration
    Flow: 1.5 mL/min
    Column Temperature: 35°C
    Injection: 10 µl
    Detector: 230 nm

    Page 2 of 8
    Representative Chromatogram from Lot: LRAA5630 Analysis

    ASSAY vs. EP CRS (as is basis)


    ASSAY VALUE vs. EP BATCH
    99.5% 3.0
    Labeled Content = None
    Assigned Content = 99.9% *
    *The assigned content of the EP CRS was determined by assay against the USP
    Reference Standard

    METHOD: HPLC (ref.: Ranitidine Hydrochloride USP34)


    Column: Ascentis C18 4.6 x 150 mm, 5um
    Mobile Phase: Solution A: Phosphate buffer, acetonitrile (98:2)
    Solution B: Phosphate buffer, acetonitrile (78:22)
    Phosphate buffer: Water, phosphoric acid, NaOH, pH 7.1
    Gradient:
    Time(minutes) Solution A % Solution B % Elution
    0 - 10 100 → 0 0 → 100 Linear gradient
    10 - 15 0 100 Isocratic
    15 - 16 0 → 100 100 → 0 Linear gradient
    16 - 20 100 0 Re-equilibration
    Flow: 1.5 mL/min
    Column Temperature: 35°C
    Injection: 10 µl
    Detector: 230 nm

    Page 3 of 8
    Representative Chromatogram from Lot: LRAA5630 Analysis

    PURITY DETERMINATION BY MASS BALANCE

    CHROMATOGRAPHIC IMPURITY ANALYSIS


    METHOD: HPLC (ref.: Ranitidine Hydrochloride USP32)
    Column: Wakosil II 5C18, 4.6 x 250mm. 5µm
    Mobile Phase: Solution A: Phosphate buffer, acetonitrile (98:2)
    Solution B: Phosphate buffer, acetonitrile (78:22)
    Phosphate buffer: Water, phosphoric acid, NaOH, pH 7.1
    Gradient:
    Time(minutes) Solution A % Solution B % Elution
    0 - 10 100 → 0 0 → 100 Linear gradient
    10 - 15 0 100 Isocratic
    15 - 16 0 → 100 100 → 0 Linear gradient
    16 - 20 100 0 Re-equilibration
    Flow: 2mL/min
    Injection: 10 µl
    Detector: 230 nm

    Impurities Detected
    USP Ranitidine Related Compound B (EP Impurity A): 0.5%

    Representative Chromatogram from Lot: LRAA5630 Impurity Analysis

    Page 4 of 8
    RESIDUAL SOLVENTS
    Method: GC-MS Headspace (ref.: Residual Solvents <467>, USP34)
    Column: DB-1301
    Carrier gas: He
    Flow: 1.2mL/min
    Split Ratio: 1:5
    Injection/Temperature: 1µl/250°C
    Temperature Program: 40°C for 20min, 10°C/min to 240°C, hold 20min

    Solvents Detected: None

    LOSS ON DRYING/VOLATILES
    Method: Vacuum at 60° for 3 hours
    Mean of three samples, Loss = 0.1%

    RESIDUE ANALYSIS
    Method: Sulfated Ash
    Sample Size: ~1 g
    Mean of three determinations, Residue = 0.01%

    CERTIFIED PURITY BY MASS BALANCE [100% - Impurities (normalized)]

    99.4% Ucrm = ±0.1%, k = 2

    Page 5 of 8
    IDENTIFICATION TESTS
    INFRARED SPECTROPHOTOMETRY (Comparative identification analysis
    demonstrates direct traceability to Pharmacopeial standards)

    Ranitidine HCl is known to exist in different polymorphic forms (form I and II). The
    FTIR spectrum of the RTP sample showed good correlation to the EP and BP samples.
    However, the USP sample is clearly a different polymorph. Visual comparison of the
    RTP and USP samples shows good correlation in the position of virtually all peaks. In
    the RTP, EP, and BP samples, the unique peak at ~1050 cm-1 is indicative that they are
    form II. In the USP sample, the unique peak at ~1550 cm-1 is indicative that it is form I.

    Page 6 of 8
    1
    H NMR (Data provided by an external laboratory; not in scope of accreditation)

    Consistent with structure

    ELEMENTAL ANALYSIS (Data provided by an external laboratory; not in scope of accreditation)


    Exeter Analytical 440 Elemental Analyzer
    Combustion method
    % Theoretical Result 1 Result 2 Mean
    C 44.50 44.80 44.77 44.79
    H 6.61 6.51 6.55 6.53
    N 15.97 16.05 15.89 15.97

    HOMOGENEITY ASSESSMENT
    Homogeneity was assessed in accordance with ISO Guide 35. Completed units were
    sampled using a random stratified sampling protocol. The results of chemical analysis
    were then compared by Single Factor Analysis of Variance (ANOVA). The uncertainty
    due to homogeneity was derived from the ANOVA. Heterogeneity was not detected
    under the conditions of the ANOVA.

    Analytical Method: HPLC Sample size: ~25mg

    Page 7 of 8
    UNCERTAINTY STATEMENT
    Uncertainty values in this document are expressed as Expanded Uncertainty (Ucrm)
    corresponding to the 95% confidence interval. Ucrm is derived from the combined
    standard uncertainty multiplied by the coverage factor k, which is obtained from a t-
    distribution and degrees of freedom. The components of combined standard uncertainty
    include the uncertainties due to characterization, homogeneity, long term stability, and
    short term stability (transport). The components due to stability are generally considered
    to be negligible unless otherwise indicated by stability studies.

    STABILITY ASSESSMENT
    Significance of the stability assessment will be demonstrated if the analytical result of the
    study and the range of values represented by the Expanded Uncertainty do not overlap the
    result of the original assay and the range of its values represented by the Expanded
    Uncertainty. The method employed will usually be the same method used to characterize
    the assay value in the initial evaluation.
    Long Term Stability Evaluation - An assessment, or re-test, versus a Compendial
    Reference Standard may be scheduled, within the 3 year anniversary date of a release of a
    Secondary Standard. The re-test interval will be determined on a case-by-case basis.
    Short Term Stability Study - It is useful to assess stability under reasonably anticipated,
    short term transport conditions by simulating exposure of the product to humidity and
    temperature stress. This type of study is conducted under controlled conditions of
    elevated temperature and humidity.

    __________________________________ _______________________________
    Operations Manager QA Supervisor

    APPENDIX

    Original Release Date: 07 July 2014

    Manufactured and certified by Sigma-Aldrich RTC, Inc.


    2931 Soldier Springs Rd, Laramie WY, USA 82070 Page 8 of 8
    (Phone): 1-307-742-5452 (Fax): 1-855-831-9212
    email: RTCTechGroup@sial.com

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