Abstract
Identification and quantification of an active adjuvant and its degradation product/s in drug formulations are important to ensure drug product safety and efficacy. QS-21 is a potent adjuvant that is currently involved in several clinical vaccine trials and a constituent of licensed vaccines against malaria and shingles. In an aqueous milieu, QS-21 undergoes pH- and temperature-dependent hydrolytic degradation to form a QS-21 HP derivative that may occur during manufacturing and/or long-term storage. Intact QS-21 and deacylated QS-21 HP elicit different immune response profiles; thus, it is imperative to monitor QS-21 degradation in vaccine adjuvant formulation. To date, a suitable quantitative analytical method for QS-21 and its degradation product in drug formulations is not available in the literature. In view of this, a new liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and qualified to accurately quantify the active adjuvant QS-21 and its degradation product (QS-21 HP) in liposomal drug formulations. The method was qualified according to the FDA Guidance for Industry: Q2(R1). Study results showed that the described method presents good specificity for QS-21 and QS-21 HP detection in a liposomal matrix, good sensitivity characterized by the limit of detection (LOD)/limit of quantitation (LOQ) in the nanomolar range, linear regressions with correlation coefficients, R2 > 0.999, recoveries in the range of 80-120%, and precise detection and quantification with % relative standard deviation (RSD) < 6% for QS-21 and < 9% for the QS-21 HP impurity assay. The described method was successfully used to accurately evaluate in-process and product release samples of the Army Liposome Formulation containing QS-21 (ALFQ).