A B S T R A C T
High-Performance Liquid Chromatography (HPLC) is one of the most powerful and widely used analytical techniques in pharmaceutical, chemical, and biological laboratories for the separation, identification, and quantification of compounds. Despite its reliability, HPLC systems often face a range of operational and analytical challenges that can compromise accuracy, precision, and reproducibility of results. Common problems such as pressure fluctuations, baseline noise, peak tailing, retention time shifts, and poor resolution frequently arise due to instrument malfunction, mobile phase inconsistencies, or column deterioration. This review aims to provide a comprehensive study on the causes, detection, and systematic resolution of these issues through an organized troubleshooting approach. Emphasis is placed on identifying the source of errors within individual system components, including the pump, injector, column, detector, and data system. Additionally, preventive maintenance practices and good laboratory techniques are discussed to minimize downtime and enhance instrument performance. The article also explores recent advancements in intelligent diagnostic systems and self-monitoring HPLC technologies that facilitate rapid fault detection. Ultimately, effective troubleshooting not only ensures reliable chromatographic performance but also contributes to the overall quality assurance of analytical methodologies.
Keywords: High-Performance Liquid Chromatography (HPLC), Malfunction, Troubleshooting, chromatographic performance, column deterioration.