Gastrointestinal Fluid Stability Assay
Creative Animodel provides stability assay to measure compound degradation in gastrointestinal fluid. Our experienced scientists, expert in metabolism studies, will help clients advance the knowledge of PK properties of therapeutic candidates by delivering consistent and high-quality data with cost-efficiency that comes from a highly automated approach.
Why Is GI Stability Important?
Oral administration is the route of choice for new drugs. After oral dosing, the compound will encounter the gastrointestinal (GI) tract, where it can be decomposed and absorbed before reaching the therapeutic sites or further metabolism. The GI fluid is a complex and dynamic mixture of components from a number of different sources. In the stomach, the drug is mixed with saliva, gastric acids, pepsinogen, and mucus secretions. Along with delivering to the duodenum, the composition of gastric fluid changes as the fluid is mixed. Some major components of GI fluid that affect the disposition of compounds include hydrogen ion concentration, lipase, and the protein-digesting enzyme pepsin. Drug candidates may be chemically unstable due to hydrolysis as a result of low pH and enzymatic degradation in the stomach or intestine, which further reduces in vivo exposure.
Figure 1. GI tract represents opportunities for drug absorption.
Drugs are barely absorbed if the compound is degraded in the stomach or intestine. In vitro testing with simulated gastric fluid and simulated intestinal fluid can help determine if a compound is stable in the stomach or intestine, respectively. The data play a guiding role in the structural modifications to improve GI stability for optimizing bioavailability and prioritization of compounds for in vivo studies.
Standard Conditions of GI Stability Assay
GI fluid stability assay aims to diagnose or to predict the stability of test compound after oral delivery. Creative Animodel provides stability studies in simulated GI fluids or natural GI fluids from animal species. Test compounds are incubated with appropriate gastric fluid or intestinal fluid at 37℃ in duplicate. After incubation, the parent compound is investigated by LC-MS/MS analysis at five-time points over 120 minutes (0, 15, 30, 60 and 120 min). The percentage of parent compound remaining in plasma is plotted at each time point, and the half-life (T½) is calculated from the obtained curve.
Figure 2. Stability result from in-house laboratory in simulated gastric fluid. Data are shown as mean ± standard deviation.
Creative Animodel provides GI fluids stability assay to specifically satisfy your drug developing profiles. Customers can require for options including compound concentrations, incubation temperature, alternative time points and additional replicates. Our skilled experts and advanced approaches guarantee an accurate estimation of the pharmacological properties of compounds in an efficient manner.
1. Di, Li, and Edward H. Kerns. Drug-like properties: concepts, structure design and methods from ADME to toxicity optimization. Academic press, 2015.
2. Deanna M. Mudie, et al. Physiological Parameters for Oral Delivery and In vitro Testing. Mol Pharm. 2010, Oct 4; 7(5): 1388–1405.