Secondary-Ion Mass Spectrometry Analysis of Pentosan Polysulfate

Abstract Pentosan polysulfate sodium (PPS) is a glycosaminoglycan mimic that is the only current active pharmaceutical ingredient (API) for the oral treatment of interstitial cystitis. PPS is an inherently complex API due to variations in chain length, backbone structure, sulfation pattern, and end group, making discriminating between batch-to-batch as well as manufacturer-to-manufacturer differences difficult. In this study, high-throughput liquid handling and time-of-flight secondary-ion mass spectrometry (ToF-SIMS) are used to enable the rapid chemical analysis (450 samples in 6 h) of small amounts (<150 ng) of PPS. Chemical discrimination between PPS produced by different manufacturers and, in one case, batch-to-batch variation of the same manufacturer were achieved. Analysis of samples using an OrbiSIMS instrument is used to provide confident, putative assignment of the discriminating ions to enable structural interpretation of the variance observed between samples. Together with analysis of samples spiked with NaSO4, free sulfate, degree of sulfation along with the sulfate pattern are implicated as key differences between manufacturers/batches. This approach is likely to be highly beneficial for the rapid quality control of PPS.