LC-MS/MS-Based Determination of Gadobutrol Residues for Pharmaceutical Cleaning Validation

The hazards of gadolinium, widely used in magnetic resonance imaging to detect pathological lesions, should not be overlooked. Due to its pharmacological effects, any contamination from gadobutrol production poses serious health risks. Therefore, it is imperative that gadobutrol residues continue to be completely removed from production equipment. This study aimed to develop and validate a highly sensitive liquid chromatography with tandem mass spectrometry (LC-MS/MS) method for the quantitative detection of gadobutrol residues on stainless-steel surfaces and to apply it in a cleaning validation study in accordance with regulatory guidelines. Swab samples were collected from production equipment surfaces after cleaning procedures. Method validation parameters such as specificity, linearity, precision, accuracy, limit of detection (LOD), and limit of quantitation (LOQ) were evaluated. Recovery studies were performed using spiked stainless-steel plates to determine recovery rates. Swab recovery data were incorporated into the analysis of actual equipment samples. The LC-MS/MS method showed excellent linearity (r² ≥ 0.9999) within the range of 5-500 ng/mL. LOD and LOQ values were 2 ng/mL and 5 ng/mL, respectively. Intraday and interday accuracy and precision were within acceptable limits. Gadobutrol was found to be stable under short-term storage and autosampler conditions. The recovery rate was calculated as 83%. A sensitive, selective, and robust analytical method was successfully developed and validated for gadobutrol. This study is the first to perform cleaning validation for gadobutrol using LC-MS/MS with such sensitivity. The findings contribute significantly to both cleaning validation and analytical method development literature in the pharmaceutical industry.