Development of a UPLC-MS/MS assay for determination of PA-PEG8-PA polymers in rat plasma coupled with [M − H]− to enhance sensitivity†

Propionic acid-polyethylene glycol-propionic acid (PA-PEG-PA) is a commonly used biocompatible polymer in drug delivery systems. Unraveling the in vivo pharmacokinetic behavior of PA-PEG-PA polymer is important for the safety evaluation of PA-PEG-PA related drug delivery systems. In this research, a highly sensitive ultra-high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) assay was developed for detection of PA-PEG₈-PA polymers in complex biological matrices. Methoxy-polyethylene glycol propionic acid polymers with 6 subunits (mPEG₆-PA) were used as the internal standard (IS). The multiple reaction monitoring (MRM) transitions at m/z 513.4 ([M − H]⁻ precursor ions) → 441.2 (fragment ions) and m/z 367.3 ([M − H]⁻ precursor ions) → 118.8 (fragment ions) were chosen to determine PA-PEG₈-PA and mPEG₆-PA, respectively. The analysis time was only 5 min for each sample. Numerous parameters like specificity, sensitivity, accuracy, precision, recoveries, matrix effects and dilution effect were validated for the developed assay. The UPLC-MS/MS assay showed excellent linearity over the range of 30–1500 ng mL⁻¹(r > 0.995). The assay was successfully applied to quantify the concentration of PA-PEG₈-PA polymers in rat plasma.