« SEPARATIONS AND PURIFICATIONS Table 9. Stability of Standard Solution Stored over 8 Days at 2°C to 8°C Timepoint (Days)
0 1 4 6 8
Mean %RSD
Timepoint (Days)
0 1 4 6 8
Mean %RSD
Ni 232.003 98.0
101.9 99.2
104.4 99.1
101.2 2.5
Cu 327.393 99.5
102.8 95.7
100.9 100.5 100.0 3.0
Zn 213.857 100.3 102.5 99.5
103.0 101.5 101.6 1.5
Fe 239.562 99.5
101.5 97.8
103.2 103.1 101.4 2.5
of the method. All acceptance criteria for the parameters evaluated were met. The generic method validation demonstrated specifi city, linearity, precision, and repeatability. The QL of the method ranges from 2.3 μg/g to 20.4 μg/g based on a 20-mg sample size. The detection limit of the method ranges from 0.05 μg/g to 1.2 μg/g based on a 20-mg sample size. The accuracy of the method is evaluated for individual pharmaceutical compounds during the product-specifi c validation along with a specifi city assessment to demonstrate a lack of matrix interference. Standard solutions are stable for at least 8 days under ambient temperatures protected from light and under refrigerated conditions. The use of a generic method has eliminated the need for a complete method validation for new compounds going forward, resulting in signifi cant savings. The generic platform technologies discussed above can be a practical approach to quickly support the early phases of drug development. Generic platform technologies can enhance effi ciencies and eliminate redundancy in method validation for similar sample matrices. Practical generic procedures can support multiple products in development in the clinical pipeline.
References 1.
2.
Ni 231.604 99.2
101.9 99.3
103.6 99.6
101.1 2.0
Cu 324.752 99.5
102.7 95.4
101.2 99.9 99.8 3.2
Zn 206.200 99.9
103.1 101.1 103.7 102.7 102.7 1.1
Fe 238.204 98.3
101.7 98.2
103.0 103.5 101.6 2.4
Condition: 2°C to 8°C
Mg 285.213 Sn 235.485 101.5 102.9 95.7
96.2
101.4 99.8
101.0 99.1 99.7 3.1
103.2 98.9
100.8 1.9
Condition: 2°C to 8°C
Mg 279.077 Sn 283.998 98.5
95.5
102.2 99.1
104.0 99.4
101.2 2.3
101.0 98.7
104.0 98.0
100.4 2.7
Pd 363.470 87.4
109.3 102.7 102.1 103.1 104.3 3.2
Pt 214.423 98.6
101.6 97.8
101.0 97.9 99.6 2.0
Ru 349.894 96.0
101.4 98.3
103.5 97.9
100.3 2.7
5. EMEA/CHMP/SWP/4446/2000, Guideline on the specifi cation limits for residues of metal catalysts or metal reagents. Committee for Medicinal Products for Human Use (CHMP). London; 21 February 2008.
6. ICH Harmonized Tripartite Guideline. Q6A—Specifi cations: Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products: Chemical Substances, Step 4 Version, 06 October 1999.
7.
The United States Pharmacopeia Convention: General chapter <1225>, Validation of compendia procedure, Rockville, MD; 2009.
Author Biographies
Ila Patel is a Sr. Research Associate in Small Molecule Pharmaceutical Sciences Department at Genentech, USA. She has over 15 years of experience in the pharmaceutical industry supporting early stage drug development in small molecules to large molecule commercial projects. Her specialization/expertise is in a wide range of spectroscopic techniques for elemental analysis by AA, ICP-OES, and ICP-MS.
The United States Pharmacopeia Convention: Draft <232> and <233>, Pharmacopeia Forum 36(1), 2010.
International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use, Guideline for Elemental Impurities Q3D, step 2b version, 26 July 2013.
3. Boss CB, Fredeen KJ. Concepts, Instrumentation and Techniques in Inductively Coupled Plasma Optical Emission Spectrometry. Shelton, CT: PerkinElmer; 2004.
4.
Patel I, Venkatramani CJ, Mistry K. Enhancing effi ciency of trace metals analysis using generic method validation by ICP-OES. Pittcon. Atlanta, GA. 2011.
C.J. Venkatramani is a senior scientist at Genentech, USA and has over 15 years of experience in the pharmaceutical industry. He was the key member of the Genentech technical team instrumental in taking gRED’s fi rst small molecule Erivedge from development to commercial. Erivedge is currently approved in several countries around the world for the treatment of advanced BCC. His areas of interests include ultra-trace analysis and multi-dimensional chromatography.
Larry Wigman is an analytical chemist by training with his doctorate from Duke University, under the direction of the late Charles Lochmuller. Larry has held various positions including: Senior Research Scientist at Pfi zer, Manager at Mylan, Associate Director at Sanofi , Principal Consultant at Regulitics LLC; and, is currently Senior Scientifi c Manager of the Small Molecule Analytical Chemistry and Quality Control (SMACQC) Department at Genentech.
www.americanpharmaceuticalreview.com | | 43
Pd 340.458 94.4
102.4 96.7 98.7 96.8 98.7 2.7
Pt 265.945 98.4
101.4 98.4
102.5 97.6
100.0 2.3
Ru 240.272 96.8
101.9 99.2
103.6 98.7
100.9 2.3
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