38


December 2010


you have to do much burning of the midnight oil to keep publishing?


Much midnight oil was burnt… the majority of my work was company confidential so could not be published. If we developed a new approach or application we then applied it to compounds/products that we could publish. I also supervised a number of PhD and MSc students and so had company in the lab during the evening and weekend sessions. In the mid 1990’s I was publishing 20 odd papers per year and with no internet – we had to send 3 copies of the papers and a floppy disk when we submitted a paper and have to wait months while the copies were posted to the reviewers etc. it’s a lot less painful now with on-line submission.


Given the high resolving power of CE, there was an interest in the use of "generic run buffers". Did you find that you could often carry out a large proportion of your applications with just one run buffer?


The use of a single set of MEEKC separating conditions has given us, and other researchers, much success. The method is able to cope with a highly diverse range of charged and neutral insoluble or soluble species. Standard buffers such as 50mM phosphate pH 2.5 and 15mM borate are also very useful generic buffers for basic and acidic drugs respectively. Generic run buffers have been commercialised for inorganic anion and metal ion analysis which has popularised these applications.


Did you enjoy giving presentations/ tutorials/workshops and get something out of them or did they sometimes just become an interference?


Transferring knowledge was vital in the early days of CE. The technical complexity and skills associated with running routine CE were not really available and so early practitioners really struggled to make CE reliable in their labs which gave the technique bad press. I enjoyed giving motivational presentations that showed that CE could provide useful data and was reliable and robust. I did get more satisfaction from the tutorials and workshops where I passed on the tricks of the trade. In particular it was gratifying when I could solve a technical issue that an attendee had struggled with.


For several years it looked as though capillary electro-chromatography (CEC) might supersede CE, perhaps being more attractive to those steeped in the ways of LC. Was this a technique with which you ever had a dalliance?


I did spend a short period of time working on CEC with one of my student – it was a painful


and expensive time. The columns were expensive, very fragile and prone to air bubble and blockages. We were fortunate to have collaboration with Norman Smith who had great CEC knowledge and enthusiasm and we did obtain some results and a publication but we did not pursue CEC any further.


I understand that your career is now more related directly to management activities - do you still maintain an involvement in research into CE?


I do still maintain a limited involvement in research. I am co-supervising a PhD student in Waterford Institute of Technology in Ireland and involved in a research program in Sao Paulo Brazil. Our research is mainly focussed on MEEKC and use of microemulsions as an eluent in HPLC for use in pharmaceutical analysis. I am also still writing “CE Currents” in LCGG magazine. I have recently published 2 papers concerning with continuous improvement (Lean Sigma) as I am concerned with that in GSK as part of my role.


There is a school of thought that CE has not lived up to expectations, at least for small molecule pharmaceutical R&D, and another that it is now an invaluable technique used for a wide range of applications. There is a school of thought that CE has not supplanted LC simply because it was developed AFTER CE and another school of thought that it has not been as widely used as it could have been because it lacks reliability and robustness. What are your thoughts? For example, in the hands of an 'expert' such as yourself, is questionable reliability and robustness simply not an issue?


It is true that CE suffered initially and was criticised as it was always compared to HPLC where equipment was more mature and reliable. There was also a wealth of experience and training to access in HPLC. This is gradually changing with CE as it is now included in many college/university courses. I believe that the use of CE for specific applications such as chiral analysis and inorganic anion and metal ion analysis is simpler, cheaper and more rapid than HPLC and other techniques and CE has found a routine niche here supported by commercial reagent kits. CE has struggled in the workhorse applications of assay and impurities for small ion molecules and HPLC continues to predominate.


Reliability and robustness have been improved significantly in recent years as equipment manufacturers have factored this into equipment design improvements.


CE will have its day though in pharmaceutical analysis and that day is dawning now… it’s in


the area of biopharmaceuticals. Biopharmaceuticals – proteins, DNA etc. is a big area of focus for traditional pharmaceutical companies such as GSK. CE methods such as isoelectric focussing are routinely used for characterisation of biopharmaceuticals and CE methods are often the first technique of choice. Bespoke instruments and kits are available for applications with built in robustness/ ruggedness – almost black-box operation. A series of inter-company collaboration on the analysis of biopharmaceuticals is part way though completion.


We thank Kevin for giving up his valuable time and, interestingly, very nicely setting up the next issue of Chromatography Today which, amongst other features, will cover the theme of ……. biopharmaceuticals.


Illustrative references for further reading:


Ryan R, Donegan S, Power J, and Altria K, Advances in the Theory and Application of MEEKC, Electrophoresis, 31 2010 755-767


Carleysmith SW, Dufton AM and Altria KD “Implementing Lean Sigma in Pharmaceutical R&D: a Review by Practitioners”, R&D Management, 39 2009 95-106


Ryan R., McEvoy E, Power J, Donegan S, Altria, KD “An Introduction to Microemulsion HPLC (MELC)”, LCGC, October (2008).


Nunnally B, Park SS, Patel K, Hong M, Zhang X, Wang S-X, Rener B, Reed-Bogan A, Salas-Solano O, Lau W, Girard M, Carnegie H, Garcia-Cañas V, Cheng KC, Zeng M, Ruesch M, Frazier R, Jochheim C, Natarajan K, Jessop K, Saeed M, Moffatt F,Madren S, Thiam S, Altria KD, A Series of Collaborations between Various Pharmaceutical Companies and Regulatory Authorities Concerning the Analysis of Biomolecules using Capillary Electrophoresis: Additional Instruments/Buffer, Chromatographia 66 (2007) 955-961


Marsh, A, Altria, K (2006) ” Use of multiplexed CE for pharmaceutical analysis”, Chromatographia 64 (5-6), 327-333.


Altria, K.D. (2003) “Enhanced pharmaceutical analysis by CE using dynamic surface coating system”, J. Pharm. Biomed. Anal. 31(3), 447-453.


Assi, KA, Clark, BJ, Altria, KD (1999) “ Enantiomeric purity determination of propranolol by capillary electrophoresis using dual cyclodextrins and a polyacrylamide-coated capillary” Electrophoresis 20(13) 2723-2725.


Altria, KD (1999) “Application of microemulsion electrokinetic chromatography to the analysis of a wide range of pharmaceuticals and excipients”, J. Chromatogr. A 844 (1-2), 371-386.


Altria, KD, Smith, NW, Turnbull, CH (1998), “Analysis of acidic compounds using capillary electrochromatography” J. Chromatogr. B 717 (1-2), 341-353.


Altria, KD (1996) “Determination of drug-related impurities by capillary electrophoresis “, J. Chromatogr. A 735 (1-2) 43-56.


Altria, KD, Simpson, CF, Bharij, AK et al. (1990) “ A gamma- ray detector for capillary zone electrophoresis and its use in the analysis of some radiopharmaceuticals” Electrophoresis 11 (9), 732-734.


Altria, KD, Simpson, CF (1988) “Analysis of some pharmaceuticals by high-voltage capillary electrophoresis” J. Pharm. Biomed. Anal. 6 (6-8), 801-807.


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