Biomarker discovery from mass spectral profiles: A combined proteomics and multivariate analysis

e u r o p e a n j o u r n a l o f p h a r m a c e u t i c a l s c i e n c e s 3 4 S ( 2 0 0 8 ) S25–S29

performed for ketoprofen and l-dopa drugs revealing different relationships and optimal model types. Geometry of polymer was suggested to be another drug release governing factor along with matrix viscosity. doi:10.1016/j.ejps.2008.02.065 O7 Improved insight into the dissolution behavior of amorphous drugs by in situ solid-state analysis Marja Savolainen a , K. Kogermann a,b , A. Heinz c , J. a,d a d Aaltonen , L. Peltonen , C.J. Strachan , J. Yliruusi a a

Division of Pharmaceutical Technology, Faculty of Pharmacy, University of Helsinki, Finland b Department of Pharmacy, University of Tartu, Estonia c School of Pharmacy, University of Otago, New Zealand d Drug Discovery and Development Technology Center (DDTC), Faculty of Pharmacy, University of Helsinki, Finland

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ing strength of the tablets decreased when the mixing time increased with all of the batches. With pilot and production scale this decrease was greater than with laboratory scale. This indicates that the results contrived in laboratory scale did not give the right mixing time for the greater scale sizes without altering the crushing strength of tablets. doi:10.1016/j.ejps.2008.02.067 RECENT TECHNOLOGIES IN METABOLOMICS, LIPIDOMICS AND PROTEOMICS O9 Biomarker discovery from mass spectral profiles: A combined proteomics and multivariate analysis Tarja Rajalahti a,b , R. Arneberg c,d , F.S. Berven e , A.C. Kroksveen e,f , M. Berle e , K.-M. Myhr a,b,g , C.A. Vedeler a,b , R.J. Ulvik e,h , O.M. Kvalheim i a

The aim of this study was to use in situ Raman spectroscopy to improve understanding of the phenomena that occur during dissolution of an amorphous model drug carbamazepine (CBZ). Amorphous CBZ samples were prepared by cooling the melt. Dissolution tests were done in phosphate buffer (pH 7.2) in a channel flow intrinsic dissolution test apparatus with a sight window for the Raman probe. CBZ dihydrate tablets were used for reference. Multivariate methods were applied to the Raman spectra to monitor the solid-state transformations occurring during dissolution. X-ray powder diffractometry was used as a reference method. The prepared amorphous CBZ sample did not exhibit a higher dissolution rate than the crystalline dihydrate, since the amorphous CBZ transformed to the dihydrate during the dissolution experiment. Based on the partial least squares discriminant analysis (PLS-DA) and partial least squares (PLS) regression analysis of the Raman spectra, the transformation proceeded via the crystalline anhydrate form. doi:10.1016/j.ejps.2008.02.066 O8 The effect of mixing time of the magnesium stearate on crushing strengths of tablets Satu Virtanen a , H. Salokangas b , J. Yliruusi a a

Division of Pharmaceutical Technology, University of Helsinki, Finland b Pharmaceutical Product Development, R&D, Orion Corporation, Espoo, Finland This study investigated the change of lubrication effect of magnesium stearate (mgst) when the mixing time and scale were altered. The crushing strengths of tablets, which were compressed from the mixed powders, were used as secondary response for lubrication effect. Binary mixtures of microcrystalline cellulose and mgst were mixed in three scales: laboratory (1 l), pilot (10 l) and production scale (80 l). Two parallel batches were mixed in every scale. The aim was to constitute a relationship between the mixing time of the powders and the crushing strength of the tablets. The crush-

Department of Clinical Medicine, University of Bergen, Norway Department of Neurology, Haukeland University Hospital, Bergen, Norway c Center for Integrated Petroleum Research, University of Bergen, Norway d Pattern Recognition Systems AS, Bergen, Norway e Institute of Medicine, University of Bergen, Norway f Institute of Molecular Biology, University of Bergen, Norway g The National Competence Centre for Multiple Sclerosis, Haukeland University Hospital, Bergen, Norway h Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway i Department of Chemistry, University of Bergen, Norway b

Cerebrospinal fluid (CSF) is a perfect source to search for new biomarkers to improve early diagnosis of neurological diseases. In the present study, MALDI-TOF mass spectrometry is used to examine the low molecular weight CSF proteome (Berven et al., 2007). Whole mass spectral profiles from patients with multiple sclerosis and orthopedic patients (controls) are then pretreated (Arneberg et al., 2007) and analyzed using multivariate techniques. Target projection has earlier been introduced as a method to transform abstract latent variables from multivariate regression into easily interpretable factors (Kvalheim et al., 1989). In this work, we have developed the approach further to provide information about variables (biomarkers) and objects (end-members) that are almost exclusively explained by the latent variable produced by target projection on PLS (partial least squares) components. Biomarker candidates are easily and reliably identified using this approach. It is also shown to reduce the risk of finding false candidates.

Reference

Arneberg, R., et al., 2007. Anal. Chem. 79, 7014. Berven, F.S., et al., 2007. Proteom. Clin. Appl. 1, 699. Kvalheim, O.M., et al., 1989. Chemom. Intell. Lab. Syst. 7, 39.

doi:10.1016/j.ejps.2008.02.068