Determination of Clidinium Bromide Related Compound A by mixed mode HPLC using Corona CAD detector – a case study

Orie Rubin, Analytical development, Global R&D, Teva Pharmaceutical Industries, Ltd., Kfar Saba, Israel (orie.rubin@teva.co.il)
Simona Katz, Analytical Development, R&d, Dexcel, Jerusalem, Israel

Most of the active pharmaceutical ingredients (API), as well as their related compounds (process impurities and degradation products), contain chromophores which allow the use of UV detector in chromatographic methods. However, there are enough cases where alternative detection techniques (non-UV detectors) are required.

Similarly, we are lucky since most of LC separations are performed in well explored and developed reversed phase (RP) mode. However, there are compounds which are too polar to elute at a reasonable retention time in RP HPLC and are also incompatible with normal phase (NP) HPLC. Such compounds require alternative separation techniques, like HILIC or “Mixed Mode”, which emerged during the last decade.

We present a case study, which describes method development for determination of Clidinium Bromide Related Compound A (as per USP TLC method). This development required both alternative separation method and detection technique since “Impurity A” is very polar and lacks chromophore. We provide not only the mindset while developing the method, but also challenges and obstacles which we had to overcome. One of the most challenging was the effect of excipients (which are, actually, the main part of the drug product) on system performance.

Key points of the development of a novel method using a mixed-mode HPLC combined with Corona CAD detector will be discussed, illustrated by examples and concluded with the lessons learned. 

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Abstract Reference & Short Personal Biography of Presenting Author

Orie Rubin is Analytical Development Team Leader at Global R&D, Teva Pharmaceuticals, Ltd. He is responsible for methods development for small molecules API and drug products in generic development and NTE (New Therapeutic Entities) at Kfar-Saba R&D site. Orie joined Teva in 2006 and worked till 2011 as a project coordinator in Generic Analytical R&D. From 2011 to 2015, Orie provided professional counselling in analytical methods, including troubleshooting, while working at Silicol Scientific Equipment, Ltd. In 2015 he returned to Teva and, since then, is involved in development of different and complex projects utilizing various analytical methods and technologies.

Orie holds a B.Sc. degree in Biochemistry from the University of Calgary, Canada and an MBA degree from the Ben Gurion University, Israel.