Certificate of Analysis

Transcription

1 Certificate of Analysis Bromazepam 7-Bromo-1,3-dihydro-5-(2-pyridinyl)-2H-1,4-benzodiazepin-2-one Catalog Number: Br Solution Lot: Expiration Date: Solvent: August 2015 Methanol Volume per Ampule: Not less than 1 ml Storage: Store in freezer. N N Intended Use: For R&D/analytical purposes only. Not suitable for human or animal consumption. Regulatory: USDEA Exempt Canadian TK # Safety: Flammable, Poison Page 1 of 6 NH O Expiration Date has been established through real time stability studies. Ampules are overfilled to ensure a minimum 1 ml volume fill. We advise laboratories to use measured volumes of this standard solution before diluting to the desired concentration. Component Bromazepam Chromatographic Purity 99.9% Certified Concentration ± mg/ml Uncertainty of the concentration is expressed as an expanded uncertainty in accordance with ISO and Guide 34 at the approximate 95% confidence interval using a coverage factor of k = 2 and has been calculated by statistical analysis of our production system and incorporates uncertainty of the purity factor, material density, and balance and weighing technique. Concentration is corrected for chromatographic purity, residual water, residual solvents and residual inorganics. Solution Standard Verification and Homogeneity Standard Verified Concentration (mg/ml) %RSD - Homogeneity Solution Lot Number Actual Results Acceptance Crtieria Actual Results Acceptance Crtieria New Lot ± 3% 0.4 3% Previous Lot G ± 3% Concentration is verified through multiple analyses and is calculated as the average of multiple analyses compared to an independently prepared calibration solution. Homogeneity of the New Lot is ensured through rigorous production process controls statistically analyzed to evaluate risk and verified by analysis. The % RSD of samples pulled from across the lot demonstrate homogeneity of the New Lot. Traceability Gravimetrically prepared using qualified balances calibrated semi-annually by Mettler Toledo using NIST traceable weights. Calibration verification performed weekly and prior to each use utilizing NIST traceable weights. Each balance has been assigned a minimum weighing by Mettler Toledo taking into consideration the balance and installed environmental conditions to ensure weighing complies with USP tolerances of no more than 0.1% relative error. Concentration is verified against an independently prepared 4-point calibration curve gravimetrically prepared using balances calibrated to NIST. In addition, each neat material utilized has been identified and thoroughly characterized through the use of multiple analytical techniques. Spectral data is provided on subsequent pages of the COA. Cerilliant certifies that this standard meets the specifications stated in this certificate and warrants this product to meet the stated acceptance criteria through the expiration/retest date when stored unopened as recommended. Product should be used shortly after opening to avoid concentration changes due to evaporation. Warranty does not apply to ampoules stored after opening. Lara Sparks, Quality Assurance Director December 8, 2011 Date

2 Page 2 of 6 Standard Solution Assay Parameters Calibration Curve Analysis Method: UV/Vis Calibration Curve: Linear Regression Wavelength: 275 nm Number of Points: 4 Slit Width: 1.0 nm Linearity (r) : Response: 0.5 s Neat Material Data Compound Name: Bromazepam Chemical Formula: C 14 H 10 N 3 OBr Compound Lot: PC CAS Number: Molecular Weight: Neat Material Characterization Summary Analytical Test Method Results Primary Chromatographic Purity by HPLC/PDA Analysis SP % Secondary Chromatographic Purity by GC/FID Analysis Identity by GC/MS Analysis SP SP % Consistent with Structure Identity by 1 H-NMR Analysis USP <761>, SP Consistent with Structure Residual Solvent Analysis by GC/FID Headspace AM1087 None Detected Residual Water Analysis by Karl Fischer Coulometry USP <921>, SP % Inorganic Content by Microash Analysis SP < 0.1% Purity Factor 99.88% Primary purity is calculated as the average of two independently performed analyses utilizing two different methods. Acceptance criteria requires the purity values to be within 0.5% of each other. The primary chromatographic purity value is used to calculate the Purity Factor. A secondary chromatographic purity method is utilized as a control. Purity Factor = [(100 - wt% residual solvent - wt% residual water - wt% residual inorganics) x Chromatographic Purity/100]. Purity factor does not include adjustment for chiral and/or isotopic purity.

3 Spectral and Physical Data Page 3 of 6 HPLC mau DAD1 C, Sig=238,8 Ref=off (LC31208\P D) m Column: Prodigy ODS 3, 4.6 x 250 mm Mobile Phase: A: Acetonitrile B: 1 mm Ammonium acetate buffer Gradient Program: Time (mins) 0 25 %A %B Flow Rate: 1.0 ml/min Wavelength: 238 nm Data File Name: Operator: Instrument: Sample Name: Method File: Acquired: C:\HPCHEM\1\DATA\LC31208\P D TNT LC#3 PC BENZO-1.M December 11, :16 PM Peak # Ret Time Area Height Area % GC/FID FID1 A, (B D) counts Column: DB-5ms, 30 m x 0.53 mm ID, 1.5 µm film thickness Temp Program: 40 C to 200 C at 40 C/min 200 C to 300 C at 5 C/min (hold 16 min) Injector Temp: Cool-on-Column Detector Temp: 325 C Data File Name: Operator: Instrument: Sample Name: Method File: Acquired: C:\HPCHEM\1\DATA\B D RPC GC#2 PC B03E.M December 11, :58 PM m Peak # Ret Time Area Height Area %

4 Spectral and Physical Data (cont.) Residual Solvent Analysis by GC/FID Headspace FID1 A, (GC91208\D D) pa N M P Page 4 of 6 Column: DB-ALC1 30 m x 0.53 mm, 3 µm film thickness Temp Program: 40 C (12 min) to 220 C at 40 C/min (5.5 min) Carrier Gas: Helium Flow Rate: 2.0 ml/min Detector Temp: 250 C Injector: Headspace Sampler Injector Temp: 200 C HS Oven Temp: 200 C Injection Volume: 1.0 ml Incubation Time: 10 minutes Data File Name: Operator: Instrument: Sample Name: Acquired: C:\CHEM32\1\DATA\GC91208\D D KRS GC#9 PC December 18, :16 PM min Peak Compound Area Weight % 1 NMP NA NA Total 0.00 ND - Not Detected 1 H NMR Instrument: Bruker DRX 400 NUMBER FROM TO VALUE PPM 8.65 PPM PPM 8.48 PPM PPM 8.01 PPM PPM 7.84 PPM PPM 7.59 PPM PPM 7.49 PPM PPM 7.40 PPM PPM 7.00 PPM PPM 4.32 PPM 2.00 Solvent: Chloroform-D PPM

5 Spectral and Physical Data (cont.) Page 5 of 6 Identity by GC/MS Analysis

6 Page 6 of 6 COA Revision History Revision No. Date Reason for Revision 00 8/31/2010 Initial version 01 12/8/2011 Revised Storage condition from "Refrigerate or freeze" to "Store in freezer."