A Liquid Chromatography High-Resolution Tandem Mass Spectrometry Method to Quantify QS-21 Adjuvant and Its Degradation Products in Liposomal Drug Formulations

Identification and quantification of an active adjuvantand itsdegradation product/s in drug formulations are important to ensuredrug product safety and efficacy. QS-21 is a potent adjuvant thatis currently involved in several clinical vaccine trials and a constituentof licensed vaccines against malaria and shingles. In an aqueous milieu,QS-21 undergoes pH- and temperature-dependent hydrolytic degradationto form a QS-21 HP derivative that may occur during manufacturingand/or long-term storage. Intact QS-21 and deacylated QS-21 HP elicitdifferent immune response profiles; thus, it is imperative to monitorQS-21 degradation in vaccine adjuvant formulation. To date, a suitablequantitative analytical method for QS-21 and its degradation productin drug formulations is not available in the literature. In view ofthis, a new liquid chromatography-tandem mass spectrometry (LC-MS/MS)method was developed and qualified to accurately quantify the activeadjuvant QS-21 and its degradation product (QS-21 HP) in liposomaldrug formulations. The method was qualified according to the FDA Guidancefor Industry: Q2-(R1). Study results showed that the described methodpresents good specificity for QS-21 and QS-21 HP detection in a liposomalmatrix, good sensitivity characterized by the limit of detection (LOD)/limitof quantitation (LOQ) in the nanomolar range, linear regressions withcorrelation coefficients, R (2) > 0.999,recoveries in the range of 80-120%, and precise detection andquantification with % relative standard deviation (RSD) < 6% forQS-21 and < 9% for the QS-21 HP impurity assay. The described methodwas successfully used to accurately evaluate in-process and productrelease samples of the Army Liposome Formulation containing QS-21(ALFQ).