Compositional analyses of a human menopausal gonadotrophin preparation extracted from urine (menotropin). Identification of some of its major impurities

Abstract

Recently, a highly purified human menopausal gonadotrophin preparation (HMG) was launched. The composition and purity of this HMG (Menopur); Ferring Pharmaceuticals) with a claimed 1:1 ratio of FSH and LH was determined. Three gonadotrophins were observed: FSH, LH and human chorionic gonadotrophin (HCG). The immunoactivity for HCG was three-fold higher than the immunoactivity for LH. Because of the longer half-life of HCG as compared with LH, about 95% of the in-vivo LH-receptor-mediated bioactivity is attributable to the presence of HCG. This is substantiated by biochemical analyses. To the best of the authors' knowledge, this relatively high amount of HCG can only be explained by assuming the addition of HCG from external sources, which is a well established practice for standardization purposes. In addition to gonadotrophins, a number of other proteins were detected. The amount of these impurities, as determined by reversed-phase high-performance liquid chromatography on a peak-area basis, is at least 30%. Therefore, it is concluded that this HMG preparation contains at most 70% gonadotrophins. Via a proteomics approach three major impurities were identified: leukocyte elastase inhibitor, protein C inhibitor, and zinc-alpha(2)-glycoprotein. On the basis of the results obtained in this study, a comparison is made with recombinant FSH.