CHLORPHENIRAMINE MALEATE CERTIFIED REFERENCE MATERIAL

Transcription

1 CHLORPHENIRAMINE MALEATE CERTIFIED REFERENCE MATERIAL N C 4 H 4 O 4 N LOT #: BCBD1314V Cl Fluka No NOMINAL WT: 500 mg CORRESPONDS TO RTC LOT: P CERTIFICATE ISSUE DATE: 7. March 2012 VERSION: BCBD1314V-3 Note: Certificates may be updated due to Compendial Lot changes or the availability of new data. Check our website at: for the most current version. EXPIRATION: SEP / 2013 (Proper Storage and Handling 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: C 16 H 19 ClN 2 C 4 H 4 O 4 MW: PHYSICAL DESCRIPTION: White powder in amber vial CAS #: HAZARDS: Read MSDS before using. Always handle as if potentially hazardous using prudent laboratory techniques. INSTRUCTIONS FOR USE: 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 LABORATORY USE ONLY as a Certified Reference Material, and NOT for use in humans or animals. Certificate of Analysis Version BCBD1314V-3 Page 1 of 6

2 TRACEABILITY ASSAY RESULTS Specification: % (USP); % (EP); dried basis DETERMINATION METHOD: HPLC (ref.: EP 6, Chlorphenamine Maleate) Instrument: Agilent 1100 Column: Wakosil C18 RS 5um, 4.6 x 250 mm Mobile Phase: Acetonitrile/Water (20:80), Ammonium dihydrogen phosphate, phosphoric acid, ph 3.0 Flow: 1.3 ml/min Injection: 20 ul Detector Wavelength: 225 nm ASSAY vs. USP REFERENCE STANDARD ASSAY VALUE Expanded Uncertainty vs. USP LOT 99.9 % ± 0.8 %, k = 2 N0G316 Labeled Content = mg/mg ASSAY vs. EP CRS ASSAY VALUE Expanded Uncertainty vs. EP BATCH 99.6 % ± 1.2 %, k = 2 1.c Labeled Content = None Assigned Content = 99.7 % * *ASSIGNED CONTENT OF EP CRS, BATCH 1.c The assigned content of the EP CRS was determined by assay against the USP Reference Standard and the BP CRS Assigned Content Expanded Uncertainty 99.7% ± 1.2 %, k = 2 ASSAY vs. BP CRS ASSAY VALUE Expanded Uncertainty vs. BP BATCH 99.4 % ± 1.0 %, k = Labeled Content = 99.5 % Certificate of Analysis Version BCBD1314V-3 Page 2 of 6

3 ASSAY BY TITRATION (ref.: USP31, EP6) Method: Dissolve in glacial acetic acid; titrate to endpoint with 0.1N perchloric acid. Mean of nine determinations: 99.2 % Expanded Uncertainty = ± 0.6 %, k = 2 PURITY DETERMINATION BY MASS BALANCE CHROMATOGRAPHIC IMPURITY ANALYSIS Specification: EP6, Chlorphenamine Maleate Impurity A: NMT 0.2% Impurities B, C, D: NMT 0.1% Unspecified Impurities: NMT 0.1% Total Impurities: NMT 0.5% Method: HPLC (ref.: EP 6, Chlorphenamine Maleate) Instrument: Agilent 1100 Column: Wakosil C18 RS 5um, 4.6 x 250 mm Mobile Phase: Acetonitrile/Water (20:80), Ammonium dihydrogen phosphate, phosphoric acid, ph 3.0 Flow: 1.3 ml/min Injection: 20 ul Detector Wavelength: 225 nm Results Impurity A (2-(4-chlorophenyl)-4-(dimethylamino)-2-[2- (dimethylamino)ethyl)]butanenitrile): 0.07 % Impurity B (2.2 -dipyridylamine): 0.1 % Impurity C ((3RS)-3-(4-chlorophenyl)-N-methyl-3-(pyridine-2-yl) propan-1-amine): 0.05 % Unidentified impurity 1: 0.1 % Unidentified impurity 2: 0.1 % Total impurities: 0.4 % LOSS ON DRYING/VOLATILES Specification: NMT 0.5 % (USP/EP) Method: 105 C, 4 hours Mean of three samples, Loss = 0.05% RESIDUE ANALYSIS (ROI) Specification: NMT 0.2% (USP); NMT 0.1% (EP) Method: Sulfated Ash Certificate of Analysis Version BCBD1314V-3 Page 3 of 6

4 Sample Size: ~1 g Mean of three determinations, Residue = 0.003% CERTIFIED VALUE BY MASS BALANCE (100%-Impurities) 99.5 % Expanded Uncertainty = ± 0.7 %, k = 2 IDENTIFICATION TESTS INFRARED SPECTROPHOTOMETRY FTIR COMPARISON OF CHLORPHENIRAMINE MALEATE Fluka RTP No USP %T EP BP cm-1 Chlorpheniramine Maleate Fluka RTP Lot: P BCBD1314V Chlorpheniramine Maleate USP Lot: N0G316 Perkin Elmer Spectrum 100 Chlorpheniramine Maleate EP Batch: 1.c Sampling: Universal ATR Chlorpheniramine Maleate BP Batch: 2864 Certificate of Analysis Version BCBD1314V-3 Page 4 of 6

5 1 H NMR (Data provided by an external laboratory) Consistent with Structure ELEMENTAL ANALYSIS (Data provided by an external laboratory) Specification: Not more than 0.3% difference between theoretical and experimental Exeter Analytical 440 Elemental Analyzer Combustion method Results of duplicate analysis: % Theoretical Experimental Mean C H N MELTING RANGE Specification: Between 130 and 135 (USP/EP) Mettler Toledo FP900 Thermosystem with FP81 Measuring Cell Mean of three measurements = C OPTICAL ROTATION Specification: to (EP) Perkin Elmer Polarimeter 343 Certificate of Analysis Version BCBD1314V-3 Page 5 of 6

6 Wavelength: 589 nm Concentration: 100 mg/ml Cell Path: 100 mm Mean of three Measurements = HOMOGENEITY ASSESSMENT Between-bottle homogeneity was assessed in accordance with ISO Guide 35. Completed units were sampled over the course of the bottling operation. Samples were taken in the following manner: the units produced in the bottling operation were divided into three chronological groups, those from the Early third, the Middle third, and the Late third (Groups). A pre-determined number of sample units were then randomly selected from each group. A subset of each group was then randomly selected for chemical analysis. The results of the chemical analysis were then compared by Single Factor Analysis of Variance (ANOVA). ANALYTICAL METHOD: HPLC (ref.: Traceability Assay) An analytical sample was prepared from each of four bottles from each Group (Early, Middle, and Late/twelve total). Sample size: ~ 25 mg Replicate (triplicate) analysis was performed on each sample. The order of replicate analyses was randomized. The between bottle standard deviation was derived from the ANOVA. No significant difference between the Groups was indicated. Heterogeneity was not detected under the conditions of the ANOVA. Certified by Reviewed by Issue Date Quality Systems THIS PRODUCT WAS DESIGNED, PRODUCED AND VERIFIED BY RTC- USA FOR ACCURACY AND STABILITY IN ACCORDANCE WITH ISO 17025:2005 (ACLASS Cert AT-1467) and ISO GUIDE 34:2009 (ACLASS Cert AR-1470). Certificate of Analysis Version BCBD1314V-3 Page 6 of 6