TY - JOUR
T1 - Evaluation of the impact of sulfobutylether7-beta-cyclodextrin on the liquid chromatography-mass spectrometry analysis of biological samples arising from in vivo pharmacokinetic studies
AU - Leong, Nathania
AU - Prankerd, Richard John
AU - Shackleford, David
AU - McIntosh, Michelle Paula
PY - 2015
Y1 - 2015
N2 - The utility of cyclodextrin (CD) complexation in improving apparent solubility of drugs in parenteral formulations is well established. Administration of these formulations delivers CD directly into the systemic circulation, and it may be necessary to demonstrate unaltered in vivo disposition of a drug coadministered with a CD. Crucial to the undertaking of such a study is the need for bioanalytical assays in which CD presence does not impact drug quantitation. This is of particular importance when assessing the potential impact of in vivo CD complexation on the urinary excretion of a drug, as CDs are predominantly eliminated via glomerular filtration, and hence are present in urine at significantly higher concentration than would be present in blood and plasma. Of 23 publications (in the past 30 years) describing preclinical and clinical assessment of drug pharmacokinetics after i.v. administration of CD-enabled formulations, only two reports clearly stated that the presence of CD had no impact on assay performance. In this work, we describe the simple process involved in (1) predicting the maximum concentrations of a modified CD, sulfobutylether7-?-CD (SBE7-?-CD), in plasma and urine samples from preclinical studies, and (2) evaluating the impact of SBE7-?-CD on the quantitative liquid chromatography-mass spectrometry analysis of rimantadine.
AB - The utility of cyclodextrin (CD) complexation in improving apparent solubility of drugs in parenteral formulations is well established. Administration of these formulations delivers CD directly into the systemic circulation, and it may be necessary to demonstrate unaltered in vivo disposition of a drug coadministered with a CD. Crucial to the undertaking of such a study is the need for bioanalytical assays in which CD presence does not impact drug quantitation. This is of particular importance when assessing the potential impact of in vivo CD complexation on the urinary excretion of a drug, as CDs are predominantly eliminated via glomerular filtration, and hence are present in urine at significantly higher concentration than would be present in blood and plasma. Of 23 publications (in the past 30 years) describing preclinical and clinical assessment of drug pharmacokinetics after i.v. administration of CD-enabled formulations, only two reports clearly stated that the presence of CD had no impact on assay performance. In this work, we describe the simple process involved in (1) predicting the maximum concentrations of a modified CD, sulfobutylether7-?-CD (SBE7-?-CD), in plasma and urine samples from preclinical studies, and (2) evaluating the impact of SBE7-?-CD on the quantitative liquid chromatography-mass spectrometry analysis of rimantadine.
UR - http://onlinelibrary.wiley.com/doi/10.1002/jps.24348/epdf
U2 - 10.1002/jps.24348
DO - 10.1002/jps.24348
M3 - Article
SN - 0022-3549
VL - 104
SP - 1561
EP - 1562
JO - Journal of Pharmaceutical Sciences
JF - Journal of Pharmaceutical Sciences
IS - 4
ER -