PHENYLEPHRINE HYDROCHLORIDE CERTIFIED REFERENCE MATERIAL

Transcription

1 PHENYLEPHRINE HYDROCHLORIDE CERTIFIED REFERENCE MATERIAL OH H 3 C H N OH HCl LOT #: BCBD1315V Fluka No NOMINAL WT: 500 mg CERTIFICATE VALIDITY DATE: 12. October 2010 VERSION: BCBD1315V-1 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 in Refrigerator/Protect from Light, keep container tightly closed. Attachment of a 20 mm aluminum crimp seal recommended for unused portions. CHEMICAL FORMULA: C 9 H 13 NO 2 HCl 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: Do not dry. 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 BCBD1315V-1 Page 1 of 6

2 TRACEABILITY ASSAY RESULTS Specification: 97.5 to 102.5% (USP); 98.5 to 101.0% (EP) DETERMINATION METHOD: HPLC (ref.: EP 6, Phenylephrine HCl; USP31, Phenylephrine HCl Injection) Instrument: Agilent 1100 Column: Exsil ODS C18, 250 x 4.6 mm, 5 µm Mobile Phase: Buffer/Acetonitrile (66:34) Buffer Solution: Water, sodium octanesulfonate, ph 2.8 with phosphoric acid Flow: 1.5 ml/min Injection: 10 µl Temperature: 45 C Detector: 215 nm ASSAY vs. USP REFERENCE STANDARD ASSAY VALUE Expanded Uncertainty vs. USP LOT 100.0% ± 0.3 %, k = 2 L0F273 Labeled Content = mg/mg ASSAY vs. EP CRS ASSAY VALUE Expanded Uncertainty vs. EP BATCH 99.9% ± 0.4 %, k = 2 2.a Labeled Content = None Assigned Content = 99.9% * *ASSIGNED CONTENT OF EP CRS, BATCH 2.a The assigned content of the EP CRS was determined by assay against the USP Reference Standard and the BP CRS Assigned Content Expanded Uncertainty 99.9% ± 0.4 %, k = 2 ASSAY vs. BP CRS ASSAY VALUE Expanded Uncertainty vs. BP BATCH 99.8% ± 0.3 %, k = Labeled Content = 100.0% Certificate of Analysis Version BCBD1315V-1 Page 2 of 6

3 ASSAY BY TITRATION (ref.: USP Phenylephrine HCl) Method: Dissolve in water, add 0.1 N Bromine and HCl. Add KI solution, titrate with 0.1 N sodium thiosulfate and add starch as endpoint is approached. Mean of six determinations: 100.8% Expanded Uncertainty = ± 1.4 %, k = 2.53 PURITY DETERMINATION BY MASS BALANCE CHROMATOGRAPHIC IMPURITY ANALYSIS Specification: EP Impurities C, E: NMT 0.1% Unspecified Impurities: NMT 0.10% Total Impurities: NMT 0.2% Method: HPLC (ref.: EP 6, Phenylephrine HCl Instrument: Agilent 1100 Column: Ascentis C18, 50 x 4.6 mm, 5µm Mobile Phase: Gradient composed of Mobile Phase A: Acetonitrile, buffer solution (10:90) Mobile Phase B: Buffer solution, Acetonitrile (10:90) Buffer Solution: Water, sodium octanesulfonate, ph 2.8 with phosphoric acid Flow: 1.5 ml/min Injection: 10 µl Temperature: 45 C Detector: 215 nm Impurities Detected Impurity E: 0.01% Unspecified Impurity: 0.01% Total (TCI): 0.02% LOSS ON DRYING/VOLATILES Specification: NMT 1.0% (USP, EP) Method: 105 C for 2 hours Mean of three samples, Loss = 0.1% RESIDUE ANALYSIS Specification: NMT 0.2% (USP); NMT 0.1% (EP) Method: Sulfated Ash Sample Size: ~1 g Mean of three determinations, Residue = 0.009% Certificate of Analysis Version BCBD1315V-1 Page 3 of 6

4 CERTIFIED VALUE BY MASS BALANCE (100% - Impurities) 99.8 % Expanded Uncertainty = ± 0.2 %, k = 2 IDENTIFICATION TESTS INFRARED SPECTROPHOTOMETRY FTIR COMPARISON OF PHENYLEPHRINE HYDROCHLORIDE RTP Fluka No USP %T EP BP cm-1 Phenylepherine HCL HCL Fluka RTP LotBCBD1315V Lot: P Perkin Elmer Spectrum 100 Phenylepherine HCL USP Lot: L0F273 Phenylepherine HCL EP Batch: 2.a Sampling: Universal ATR Phenylepherine HCL BP Batch: 2701 Certificate of Analysis Version BCBD1315V-1 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 POINT Specification: Between 140 C and 145 C (USP); about 143 C (EP) Mettler Toledo FP900 Thermosystem with FP81 Measuring Cell Mean of three measurements = C OPTICAL ROTATION Specification: Specific Rotation between -42 and (USP) Perkin Elmer Polarimeter 343 Wavelength: 589 nm Concentration: 50 mg/ml Cell Path: 100 mm Mean of three Measurements = Certificate of Analysis Version BCBD1315V-1 Page 5 of 6

6 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.: 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 Validity 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 BCBD1315V-1 Page 6 of 6