Certificate of Analysis

Transcription

1 Certificate of Analysis IS GUIDE 34 ANAB Cert# AR-1470 IS/IEC ANAB Cert# AT-1467 CLARITHRMYCIN CERTIFIED REFERENCE MATERIAL H 3 C H H 3 C H 3 C H H N H CERTIFIED PURITY: 97.3%, U crm = ±0.9% k = 2 (Mass Balance/as is basis) NMINAL PACKAGE SIZE: 500mg CATALG #: PHR1038 LT #: LRAA8966 CERTIFICATE VERSIN: LRAA ISSUE DATE: 02 September 2015 Note: Certificates may be updated due to Pharmacopeial Lot changes or the availability of new data. Check our website at: for the most current version. CRM EXPIRATIN: 31 December 2020 (Proper Storage and Handling Required). RECEIPT DATE: Note: this space is provided for convenience only and its use is not required. STRAGE: Store in a Freezer, keep container tightly closed. Attachment of a 20mm aluminum crimp seal recommended for unused portions. CHEMICAL FRMULA: C 38 H 69 N 13 MW: PHYSICAL DESCRIPTIN: White powder in amber vial CAS #: Page 1 of 8

2 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. INSTRUCTINS FR USE: Do not dry, use as is. Hygroscopic. The internal pressure of the container may be slightly different from the atmospheric pressure at the user s location. pen 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: 96.0% to 102% (USP) METHD: HPLC (ref.: Clarithromycin, USP36) Column: Ascentis Express C18, 4.6 x 50mm, 2.7µm Mobile Phase A: 4.76 g/l monobasic potassium phosphate, ph 4.4 Mobile Phase B: Acetonitrile Gradient: Time (minutes) % Solution A % Solution B Flow 0.8mL/min Column Temperature: 40 C Injection 5µl Detector: 205 nm ASSAY vs. USP REFERENCE STANDARD (as is basis) ASSAY VALUE vs. USP LT 97.6% H0H380 Labeled Content = 988µg/mg Representative Chromatogram from Lot: LRAA8966 USP Analysis Page 2 of 8

3 Column: Ascentis C18, 4.6 x 50mm, 5µm Mobile Phase A: 4.76 g/l monobasic potassium phosphate, ph 4.4 Mobile Phase B: Acetonitrile Gradient: Time (minutes) % Solution A % Solution B Flow 1.1 ml/min Column Temperature: 40 C Injection 10 µl Detector: 205 nm ASSAY vs. EP CRS (as is basis) ASSAY VALUE vs. EP BATCH 95.8% 3.0 Labeled Content = 97.7% Representative Chromatogram from Lot: LRAA8966 EP Analysis ASSAY vs. BP CRS (as is basis) ASSAY VALUE vs. BP BATCH 96.4% 2964 Labeled Content = 96.0% Page 3 of 8

4 Representative Chromatogram from Lot: LRAA8966 BP Analysis PURITY DETERMINATIN BY MASS BALANCE CHRMATGRAPHIC IMPURITY ANALYSIS METHD: HPLC (ref.: Clarithromycin, USP32/EP6) See BP ASSAY Impurities Detected (Identified from EP Clarithromycin for Peak Identification CRS): Impurity A: 0.4% Impurity B: 0.2% Impurity E: 0.5% Impurity F: 0.5% Impurity P: 0.2% Impurity G: 0.1% Impurity H: 0.03% Total Impurities: 1.9% RESIDUAL SLVENTS 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 Page 4 of 8

5 WATER DETERMINATIN Method: Karl Fisher titration Mean of three measurements, Water Content = 0.7% RESIDUE ANALYSIS Method: Sulfated Ash Sample Size: ~0.5g Mean of three measurements, Residue = 0.1% CERTIFIED PURITY BY MASS BALANCE [100% - Impurities (normalized)] IDENTIFICATIN TESTS 97.3% U crm = ±0.9%, k = 2 INFRARED SPECTRPHTMETRY (Comparative identification analysis demonstrates direct traceability to Pharmacopeial standards) Page 5 of 8

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7 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 H N PTICAL RTATIN Specification: Between -94 and -102 (USP/EP) Perkin Elmer Polarimeter 343 Wavelength: 589 nm Concentration: ~1 mg/ml in Methylene Chloride Cell Path: 100 mm Mean of three Measurements = Page 7 of 8

8 HMGENEITY ASSESSMENT Homogeneity was assessed in accordance with IS 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 (ANVA). The uncertainty due to homogeneity was derived from the ANVA. Heterogeneity was not detected under the conditions of the ANVA. Analytical Method: HPLC Sample size: ~75mg UNCERTAINTY STATEMENT Uncertainty values in this document are expressed as Expanded Uncertainty (U crm ) corresponding to the 95% confidence interval. U crm 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. perations Manager QA Supervisor APPENDIX riginal Release Date: 02 September 2015 Manufactured and certified by Sigma-Aldrich RTC, Inc Soldier Springs Rd, Laramie WY, USA (Phone): (Fax): RTCTechGroup@sial.com Page 8 of 8