Glasdegib, A Hedgehog Signaling Inhibitor Quantification by Development of Validated LC-ESI-MS/MS (QTRAP) Method in Human Plasma

Abstract

Cancer medication Glasdegib, created by Pfizer, has FDA approval. It serves as a tiny molecule an inhibitor of sonic hedgehog, a protein that is overexpressed in several cancer types. Like the majority of medications in its class, it inhibits the smoothened form that contains the hedgehog's sonic receptor (SMO). Clinical trials in phase II are ongoing in four instances. One is testing glasdegib's ability to treat myelofibrosis in patients whose condition was resistant to ruxolitinib treatment. We're aware of no method for precisely measuring Glasdegib, an anti-cancer medication, in biological fluids at the moment. A novel, simple& robust LC-MS/MS method was developed in to detect Glasdegib in a biological fluid. Here, we came up with a novel bioanalytical method using isocratic elution with a symmetric C18 column (150 x 4.6 mm, 3.5 µm), acn: 0.1% formic acid (30:70) was used as mobile phase pH of the mobile phase was adjusted to 4.0 using 0.1% formic acid at rate of flow for 1 ml/min. The drug retention was found as 2.622 minutes, and the total analysis time was set for 6 minutes. The Glasdegib calibration curve was drawn at concentrations ranging from 6 ng to 120 ng/ml of Glasdegib, with regression coefficient (r2) of 0.999. System suitability parameters for resolution, tailing factor and theoretical plates, are found in acceptable limits. The recovery studies indicated that 99.94% of the drug can be extracted using the developed method in an acceptable ratio. The results of the matrix effect study show that the matrix has no impact on recovery; the result is 98.55%, and some other validation parameters are accuracy, linearity, robustness, LOD and LOQ are found in acceptable limits. The developed method should follow an analytical approach like precise, sensitive, and accurate for the evaluation of Glasdegib in biological matrix. The results of the accelerated stability studies reveal that the drug is stable under various conditions, according to USFDA Guidelines.