Camilla Svanström

Active Biotech, Lund, Skåne, Sweden

Are you Camilla Svanström?

Claim your profile

Publications (2)5.23 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The metabolic conversion of midazolam (MDZ) to its main metabolite 1'-hydroxy-midazolam (1-OH-MDZ) can be used as a probe drug for cytochrome P450 3A (CYP3A) activity. A sensitive method for the simultaneous determination of MDZ and its metabolite 1-OH-MDZ in human plasma using supported liquid extraction (SLE) in combination with liquid chromatography-tandem mass spectrometry (LC-MS/MS) detection was developed and validated. Plasma samples (100 μL) were diluted with 0.5M NH(3) (aq) containing deuterated internal standards. The samples were extracted with ethyl acetate on a 96-well SLE-plate. Separation was performed on a Symmetry Shield RP18 column using an acidic gradient running from 2% to 95% methanol in 3 min. Detection was performed using a triple quadrupole mass spectrometer running in positive electrospray selected reaction monitoring (SRM) mode. The validated dynamic range was 0.2-100 nmol/L for both analytes. In the concentration range 0.6-75 nmol/L the extraction recoveries were in the ranges 91.2-98.6% and 94.5-98.3% for MDZ and 1-OH-MDZ, respectively. Matrix effects were more pronounced for MDZ than for 1-OH-MDZ but the response was still 75.4% or higher compared to a reference. The overall repeatability was within 2.2-7.6% for both analytes, the overall reproducibility was within 3.1-10.2% for both analytes and the overall accuracy bias was within -1.1 to 7.5% for both analytes. The method was successfully applied to determine the plasma concentrations of MDZ and 1-OH-MDZ in 14 healthy volunteers up to 24h after administration of a single oral dose of 2mg MDZ. The SLE technology was found to be convenient and suitable for sample preparation, and the developed method was found to be rapid, selective and reproducible for the simultaneous determination of MDZ and 1-OH-MDZ in human plasma.
    Journal of pharmaceutical and biomedical analysis 01/2012; 58:71-7. · 2.45 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Tasquinimod (ABR-215050) is an oral drug in clinical development for treatment of patients with castrate resistant prostate cancer. This paper describes a method for the determination of tasquinimod in human plasma. The method is based on liquid chromatography (LC) coupled to tandem mass spectrometry (MS/MS) using stable isotope labeled tasquinimod as internal standard (IS). The plasma samples were processed by protein precipitation using acidic acetonitrile containing the IS. The precipitated samples were centrifuged and the supernatant was injected directly into the LC-MS/MS system. Chromatographic separation was performed on a reversed phase column using fast gradient elution, with a total run cycle time of 4 min. The method was validated with respect to accuracy, precision, dynamic range, lower limit of quantification, selectivity and robustness. Furthermore, the stability of tasquinimod in spiked plasma, in processed extracts and in incurred samples was thoroughly studied. The method was validated in the range of 1.0-2400 nmol/L, defining the lower and upper limits of quantification. The repeatability, reproducibility and overall bias were 1.5-7.1%, 3.5-7.4%, and 1.3-4.7%, respectively, in the range of 1-2000 nmol/L. Excellent selectivity was demonstrated in the validation, as well as in study samples from both healthy volunteers and cancer patients. Robustness was demonstrated by the calculated carry-over as low as 0.06%, and by an incurred sample reproducibility (ISR) experiment where 97% of the reanalyzed samples fulfilled the acceptance criteria of 20% deviation from initial analysis result. Also, tasquinimod was found to be stable in all investigated matrices, including in incurred samples. In an incurred sample stability (ISS) investigation, tasquinimod was demonstrated to be stable for 24 months, and 97% of the reanalyzed samples were within 20% from the initial analysis result. In conclusion, the method was demonstrated to be accurate, precise, robust and reliable for the determination of tasquinimod. The method was successfully used in several clinical studies for the support of pharmacokinetic and pharmacodynamic evaluations.
    Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 09/2011; 879(30):3401-6. · 2.78 Impact Factor