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  • 1.
    Hellberg, Emma
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Westberg, Annica
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Appelblad, Patrik
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Advanced Analytical, Merck Life Science AS, Oslo, Norway.
    Mattsson, Sofia
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Evaluation of dissolution techniques for orally disintegrating mini-tablets2021In: Journal of Drug Delivery Science and Technology, ISSN 1773-2247, Vol. 61, article id 102191Article in journal (Refereed)
    Abstract [en]

    Mini-tablets are suitable for paediatric as well as geriatric use since they may provide flexible and accurate dosing and administration. Due to the minute tablet size, there is a need for new standardized quality evaluation procedures and conventional techniques may have to be adopted. The main objective of the study was to evaluate different dissolution techniques for orally disintegrating mini-tablets. Dissolution tests using mini-paddle apparatus were compared with standard size paddle apparatus, and the effect of paddle rotation speed was evaluated. Also, the filter choice, and its impact on dissolution, was considered. Sodium salicylate was used as a model drug substance and was mixed with different size fractions of mannitol. The powder mixtures were compacted into 2 mm flat faced tablets. The mini-tablets were characterized regarding weight and content uniformity, tensile strength, friability, disintegration and dissolution. Similar dissolution profiles were obtained with both mini and standard equipment. The paddle rotation speed affected the dissolution profiles; a low paddle speed resulted in a slower dissolution. Furthermore, choosing a chemically inert filter will increase the likelihood of obtaining reliable and accurate results. An appropriately designed dissolution test using mini-paddle apparatus is required prior to further implementation in quality control procedures.

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  • 2.
    Kong, Ziqing
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Jia, Shaodong
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Chabes, Anna Lena
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Appelblad, Patrik
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology. Merck Chemicals and Life Science AB, Solna, Sweden.
    Lundmark, Richard
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Moritz, Thomas
    Chabes, Andrei
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Simultaneous determination of ribonucleoside and deoxyribonucleoside triphosphates in biological samples by hydrophilic interaction liquid chromatography coupled with tandem mass spectrometry2018In: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962, Vol. 46, no 11, article id e66Article in journal (Refereed)
    Abstract [en]

    Information about the intracellular concentration of dNTPs and NTPs is important for studies of the mechanisms of DNA replication and repair, but the low concentration of dNTPs and their chemical similarity to NTPs present a challenge for their measurement. Here, we describe a new rapid and sensitive method utilizing hydrophilic interaction liquid chromatography coupled with tandem mass spectrometry for the simultaneous determination of dNTPs and NTPs in biological samples. The developed method showed linearity (R2 > 0.99) in wide concentration ranges and could accurately quantify dNTPs and NTPs at low pmol levels. The intra-day and inter-day precision were below 13%, and the relative recovery was between 92% and 108%. In comparison with other chromatographic methods, the current method has shorter analysis times and simpler sample pre-treatment steps, and it utilizes an ion-pair-free mobile phase that enhances mass-spectrometric detection. Using this method, we determined dNTP and NTP concentrations in actively dividing and quiescent mouse fibroblasts.

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  • 3. Marrubini, Giorgio
    et al.
    Dugheri, Stefano
    Cappelli, Giovanni
    Arcangeli, Giulio
    Mucci, Nicola
    Appelblad, Patrik
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Advanced Analytical, Merck Life Science AS, 0277, Oslo, Norway.
    Melzi, Camillo
    Speltini, Andrea
    Experimental designs for solid-phase microextraction method development in bioanalysis: A review2020In: Analytica Chimica Acta, ISSN 0003-2670, E-ISSN 1873-4324, Vol. 1119, p. 77-100Article, review/survey (Refereed)
    Abstract [en]

    This review is an update of a previous review in 2009 and covers publications from 2009 to 2019. The review focuses on experimental design, referred to as the design of experiments (DoE), used in developing bioanalytical solid-phase microextraction (SPME) methods. Characteristics of different SPME approaches are illustrated and critically discussed. The literature selection evidences that two-level full factorial designs, with a limited number of factors (<5), are most frequently used for preliminary factors screening. When applying the response surface methodology for the quantitative assessment of factorial effects, few quadratic models were used. The most popular were the rotatable central composite and Box-Benkhen designs. Models including more than four factors, such as fractional factorial designs (including the Plackett-Burman and Taguchi designs), were rarely used. Definitive screening and D-Optimal designs were not reported anywhere in the literature selection. When examining the diagnostic criteria used to evaluate different model's quality and validity, it was apparent the researchers relied heavily on commercial software for experimental design, analysis, and reporting of the results. 

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