“…The collected blood samples were centrifuged for 15 min at 2800g and stored at À70 C. For organ collection, the animals were culled with deep isoflurane anesthesia, and heart, adipose tissue, bone, kidney, and brain were harvested separately, homogenized in PBS (0.1 mM, pH 7.4, 1:10), and stored at À70 C for further analysis. The tissues were homogenized per the procedure reported by Hong Gao and John Williams (Gao & Williams, 2019).…”
Section: Pharmacokinetic and Tissue Distribution Studiesmentioning
A bioanalytical method for the quantification of rosiglitazone in rat plasma and tissues (adipose tissue, heart, brain, bone, and kidney) using LC–MS/MS was developed and validated. Chromatographic separation was achieved on a Gemini C18 column (50 × 4.6 mm, 3 μm) using a mobile phase consisting of 10 mM ammonium formate (pH 4.0) and acetonitrile (10:90, v/v) at a flow rate of 0.8 mL/min and injection volume of 10 μL (internal standard: pioglitazone). LC–MS detection was performed with multiple reaction monitoring mode using target ions at m/z → 358.0 and m/z → 357.67 for rosiglitazone and pioglitazone (internal standard), respectively. The calibration curve showed a good correlation coefficient (r2) over the concentration range of 1–10,000 ng/mL. The mean percentage recoveries of rosiglitazone were found to be over the range of 92.54–96.64%, with detection and lower quantification limit of 0.6 and 1.0 ng/mL, respectively. The developed method was validated per U.S. Food and Drug Administration guidelines and successfully utilized to measure rosiglitazone in plasma and tissue samples. Further, the developed method can be utilized for validating specific organ‐targeting delivery systems of rosiglitazone in addition to conventional dosage forms.
“…The collected blood samples were centrifuged for 15 min at 2800g and stored at À70 C. For organ collection, the animals were culled with deep isoflurane anesthesia, and heart, adipose tissue, bone, kidney, and brain were harvested separately, homogenized in PBS (0.1 mM, pH 7.4, 1:10), and stored at À70 C for further analysis. The tissues were homogenized per the procedure reported by Hong Gao and John Williams (Gao & Williams, 2019).…”
Section: Pharmacokinetic and Tissue Distribution Studiesmentioning
A bioanalytical method for the quantification of rosiglitazone in rat plasma and tissues (adipose tissue, heart, brain, bone, and kidney) using LC–MS/MS was developed and validated. Chromatographic separation was achieved on a Gemini C18 column (50 × 4.6 mm, 3 μm) using a mobile phase consisting of 10 mM ammonium formate (pH 4.0) and acetonitrile (10:90, v/v) at a flow rate of 0.8 mL/min and injection volume of 10 μL (internal standard: pioglitazone). LC–MS detection was performed with multiple reaction monitoring mode using target ions at m/z → 358.0 and m/z → 357.67 for rosiglitazone and pioglitazone (internal standard), respectively. The calibration curve showed a good correlation coefficient (r2) over the concentration range of 1–10,000 ng/mL. The mean percentage recoveries of rosiglitazone were found to be over the range of 92.54–96.64%, with detection and lower quantification limit of 0.6 and 1.0 ng/mL, respectively. The developed method was validated per U.S. Food and Drug Administration guidelines and successfully utilized to measure rosiglitazone in plasma and tissue samples. Further, the developed method can be utilized for validating specific organ‐targeting delivery systems of rosiglitazone in addition to conventional dosage forms.
“…However, the probe and the blades need to be thoroughly and repeatedly cleaned between each use to avoid cross‐contamination. Mechanical homogenization can cause heat; a good practice is to ensure the samples stay cool on ice during processing (Gao & Williams, 2019; Liang et al, 2011).…”
Toxicokinetics (TK) is an integral part of nonclinical (preclinical) safety assessment of small-molecule new chemical entities in drug development. It is employed to describe the systemic exposure of a drug candidate and/or its important metabolite(s) achieved in study animals and elucidate the relationship (proportional, over-proportional, or under-proportional) between systemic exposure and dose administered and the associated differences/similarities between male and female animals along with the possible accumulation/induction. TK data and the derived parameters are employed to propose safe starting doses for clinical use of the new drug candidate through proper extrapolation of findings in study animals to humans. This review has attempted to highlight the health authority expectations on TK assessment in supporting preclinical safety profiling of new chemical entities. A robust TK assessment requires good understanding of absorption, distribution, metabolism, and elimination processes of drug candidate, adequate TK sampling (e.g., controls where relevant), implementation of fit-for-purpose bioanalytical methods (validated or scientifically qualified) along with necessary measures to prevent mis-dosing or ex vivo contamination, and establishment of stability of the drug candidate and/or its metabolite(s) in the intended species matrix to ensure the reliability of bioanalytical and TK data. The latter provides a vital link between animal experiments and human safety.
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