Clinical in use studies is key deliverable to ensure product quality and patient safety during drug administration in clinical setting. As a result of potency and/or bioavailability restrictions, many of parenteral drugs are administered intravenously and the variety of ancillary components available in the market poses many challenges. One of the key targets of intravenous administration is sterility of dose solution to ensure patient safety. To achieve the sterile administration at the use of in-line filter is deemed necessary for IV infusions. This raises many challenges such as filter adsorption and drug product compatibility. In addition, the drug product is usually further diluted to achieve the target dose concentration for administration. As a result of further dilution of drug product, diluent compatibility raises many analytical challenges by impacting sample matrix, sample concentration and column chemistry. A practical approach is shown here to overcome in-line filter adsorption challenges. Furthermore, various different sample preparation techniques and method modifications approaches are shown to overcome in-use analytical challenges.