LCGC Europe
Wouldn’t it be nice if a single generic high performance liquid chromatography (HPLC) method could be used for all small molecule drugs - not only for potency assays but also for ICH-compliant stability-indicating assays?
Wouldn’t it be nice if a single generic high performance liquid chromatography (HPLC) method could be used for all small molecule drugs - not only for potency assays but also for ICH-compliant stability-indicating assays?
The use of generic HPLC methods in pharmaceutical analysis is not new. For at least two decades, generic HPLC/UV/mass spectrometry (MS) methods using 1–2 min ballistic gradients have been used successfully for high-throughput screening of combinatorial libraries and new drug candidates (1). Similar generic methods are also used for in-process control (IPC) analysis to support organic synthesis or in quality control of raw materials (2).
The latest advances in ultrahigh-pressure liquid chromatography (UHPLC) systems and column technologies have enabled the development of a versatile, generic reversed-phase method(s) amenable to multiple small-molecule new chemical entities (NCEs) with an analysis time of 2 min for cleaning verification (3–4). The same universal methodology was found applicable for rapid characterization (3–6 min) of many drug substance samples with peak capacities over 200 and provides a useful starting point for the development of ICH-compliant stability-indicating assays of most small-molecule NCEs.
In this upcoming keynote presentation in HPLC 2019 in Milan, I will describe the development of this universal generic method(s) by selecting the best column technologies with optimized operating conditions for pharmaceutical analysis (superficially porous particles with bonding chemistries most compatible to highly basic compounds with simple mobile phases) (see Figure 1). The rationales used in the justification of the selection of various parameters will be disclosed.
Figure 1: The separation of 12 NCEs using the proposed universal generic gradient HPLC method.
Case studies to illustrate the versatility of this generic method approach by simple adjustments of gradient range and time in the development of stability-indicating assays will be presented. These examples will include quality assessments of many NCEs including complex drug molecules with multiple chiral centres as shown in Figure 2.
Figure 2: The separation of a retention marker solution containing a complex NCE with three chiral centres spiked with expected impurities and degradation products (including two diastereomers). The 5-min method was obtained by adjustments of gradient parameters from the universal generic method, which took only one hour.
References
Michael W. Dong is a principal consultant in MWD Consulting focused on consulting and training services in HPLC and UHPLC, pharmaceutical analysis, and drug quality. He was formerly a Senior Scientist at Genentech, Research Fellow at Purdue Pharma, and Staff Scientist at Applied Biosystems / PerkinElmer. He holds a Ph.D. in analytical chemistry from the City University of New York, USA. He has 120+ publications including a bestselling book on chromatography (Modern HPLC for Practicing Scientists, Wiley). He is an editorial advisory board member of LCGC, American Pharmaceutical Review, and Chinese American Chromatography Association.
2024 EAS Awardees Showcase Innovative Research in Analytical Science
November 20th 2024Scientists from the Massachusetts Institute of Technology, the University of Washington, and other leading institutions took the stage at the Eastern Analytical Symposium to accept awards and share insights into their research.
Inside the Laboratory: The Richardson Group at the University of South Carolina
November 20th 2024In this edition of “Inside the Laboratory,” Susan Richardson of the University of South Carolina discusses her laboratory’s work with using electron ionization and chemical ionization with gas chromatography–mass spectrometry (GC–MS) to detect DBPs in complex environmental matrices, and how her work advances environmental analysis.
AI and GenAI Applications to Help Optimize Purification and Yield of Antibodies From Plasma
October 31st 2024Deriving antibodies from plasma products involves several steps, typically starting from the collection of plasma and ending with the purification of the desired antibodies. These are: plasma collection; plasma pooling; fractionation; antibody purification; concentration and formulation; quality control; and packaging and storage. This process results in a purified antibody product that can be used for therapeutic purposes, diagnostic tests, or research. Each step is critical to ensure the safety, efficacy, and quality of the final product. Applications of AI/GenAI in many of these steps can significantly help in the optimization of purification and yield of the desired antibodies. Some specific use-cases are: selecting and optimizing plasma units for optimized plasma pooling; GenAI solution for enterprise search on internal knowledge portal; analysing and optimizing production batch profitability, inventory, yields; monitoring production batch key performance indicators for outlier identification; monitoring production equipment to predict maintenance events; and reducing quality control laboratory testing turnaround time.
Infographic: Be confidently audit ready, at any time and reduce failures in pharma QC testing
November 20th 2024Discover how you can simplify the audit preparation process with data integrity dashboards that provide transparency to key actions, and seamlessly track long-term trends and patterns, helping to prevent system suitability failures before they occur with waters_connect Data Intelligence software.
Critical Role of Oligonucleotides in Drug Development Highlighted at EAS Session
November 19th 2024A Monday session at the Eastern Analytical Symposium, sponsored by the Chinese American Chromatography Association, explored key challenges and solutions for achieving more sensitive oligonucleotide analysis.