Comprehensive Analysis of Purity and Glycosylation Status of Chinese Marketed Recombinant and Urinary FSHs

Author(s): Yanbin Wang, Huan Shen*, Li Jiang, Shuo Chen, Ning Chen

Journal Name: Current Pharmaceutical Analysis

Volume 16 , Issue 6 , 2020

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Graphical Abstract:


Background: Urinary or recombinant Follicle-Stimulating Hormones (uFSH and rhFSH) are regularly applied in controlled ovarian stimulation procedure of assisted reproductive technology. Specific activity and purity of these reagents are of great importance since subtle variations in the contents and glycosylation status of FSH may result in differences in clinical efficacy and safety.

Objective: The purpose of this study was to comprehensively analyze the FSH contents, glycosylation status and non-specific protein components of the widely used rhFSH Gonal-F and two Chinese marketed FSHs, r-FSH (JSH) and urinary-derived FSH (LSB).

Methods: FSH contents, glycosylation status, and other protein contents in these FSH products were assessed with benchtop assays including SDS-PAGE, HPLC and MALDI-MS.

Results: HPLC results showed that the purity of the three products was 81.5±0.06% for Gonal-F, 79.6±0.25% for LSB and 76.5±0.36% for JSH, respectively. In addition, MALDI-MS analysis demonstrated that the Gonal-F contained more types of glycosylated isoforms compared to the local rFSHs. The analytical assessment showed that the urinary-derived FSH contained several other protein components.

Conclusion: These results suggest that rhFSH Gonal-F is with high purity and potential high activity.

Keywords: Follicle-stimulating hormones, recombinant, urinary, purity, glycosylation, protein components.

Kobori, Y.; Suzuki, K.; Iwahata, T.; Shin, T.; Sato, R.; Nishio, K.; Yagi, H.; Arai, G.; Soh, S.; Okada, H. Induction of spermatogenesis by rhFSH for azoospermia due to spermatogenic dysfunction with maturation arrest: five case series. Syst Biol Reprod Med, 2015, 61(3), 168-170.
[] [PMID: 25804205]
Yang, S.; Shen, Y.; Niu, Y.; Hildebrandt, T.B.; Jewgenow, K.; Goeritz, F.; He, X.; Zhou, Q.; Ji, W. Effects of rhFSH regimen and time interval on ovarian responses to repeated stimulation cycles in rhesus monkeys during a physiologic breeding season. Theriogenology, 2008, 70(1), 108-114.
[] [PMID: 18456315]
Follitropin-alpha. Follitropin-alpha. Follitropin-alpha, Gonal-F, recombinant human follicle-stimulating hormone (Ares-Serono), SJ 0021, rh-FSH, rhFSH (Ares-Serono). Drugs R D., 1999, 2(6), 423-424.
[PMID: 10763457]
Liu, X.; Hao, C.; Wang, J. Efficacy of highly purified urinary FSH versus recombinant FSH in chinese women over 37 years undergoing assisted reproductive techniques. Int. J. Fertil. Steril., 2015, 8(4), 385-392.
[PMID: 25780520]
Levi Setti, P.E.; Alviggi, C.; Colombo, G.L.; Pisanelli, C.; Ripellino, C.; Longobardi, S.; Canonico, P.L.; De Placido, G. Human recombinant follicle stimulating hormone (rFSH) compared to urinary human menopausal gonadotropin (HMG) for ovarian stimulation in assisted reproduction: a literature review and cost evaluation. J. Endocrinol. Invest., 2015, 38(5), 497-503.
[] [PMID: 25480425]
Daya, S. Updated meta-analysis of recombinant follicle-stimulating hormone (FSH) versus urinary FSH for ovarian stimulation in assisted reproduction. Fertil. Steril., 2002, 77(4), 711-714.
[] [PMID: 11937121]
van Wely, M.; Bayram, N.; van der Veen, F. Recombinant FSH in alternative doses or versus urinary gonadotrophins for ovulation induction in subfertility associated with polycystic ovary syndrome: a systematic review based on a Cochrane review. Hum. Reprod., 2003, 18(6), 1143-1149.
[] [PMID: 12773438]
Amirzargar, M.A.; Yavangi, M.; Basiri, A.; Hosseini Moghaddam, S.M.; Babbolhavaeji, H.; Amirzargar, N.; Amirzargar, H.; Moadabshoar, L. Comparison of recombinant human follicle stimulating hormone (rhFSH), human chorionic gonadotropin (HCG) and human menopausal gonadotropin (HMG) on semen parameters after varicocelectomy: a randomized clinical trial. Iran. J. Reprod. Med., 2012, 10(5), 441-452.
[PMID: 25246910]
Alothman, Z.; Rahman, N.; Raza Siddiqui, M. Review on Pharmaceutical Impurities. Stability Studies and Degradation Products: An Analytical Approach., 2013, 2, 155-166.
Siddiqui, M.R.; AlOthman, Z.A.; Rahman, N. Analytical techniques in pharmaceutical analysis: A review. Arab. J. Chem., 2017, 10, S1409-S1421.
Rahman, N.; Azmi, S.; Wu, H-F. The importance of impurity analysis in pharmaceutical products: An integrated approach. Accredit. Qual. Assur., 2006, 11, 69-74.
Liu, X.; Andoh, K.; Mizunuma, H.; Kamijo, T.; Kikuchi, N.; Yamada, K.; Ibuki, Y. Effects of recombinant human FSH (rhFSH), urinary purified FSH (uFSH), and hMG on small preantral follicles and tertiary follicles from normal adult and androgen-sterilized female mice. Fertil. Steril., 2000, 73(2), 372-380.
[] [PMID: 10685546]
Bousfield, G.R.; Butnev, V.Y.; White, W.K.; Hall, A.S.; Harvey, D.J. Comparison of follicle-stimulating hormone glycosylation microheterogenity by quantitative negative mode nano-electrospray mass spectrometry of peptide-N glycanase-released oligosaccharides. J. Glycomics Lipidomics, 2015, 5(1), 129.
[] [PMID: 25960929]
Smitz, J.; Wolfenson, C.; Chappel, S.; Ruman, J. Follicle-stimulating hormone: a review of form and function in the treatment of infertility. Reprod. Sci., 2016, 23(6), 706-716.
[] [PMID: 26446000]
Andersen, C.Y.; Westergaard, L.G.; van Wely, M. FSH isoform composition of commercial gonadotrophin preparations: a neglected aspect? Reprod. Biomed. Online, 2004, 9(2), 231-236.
[] [PMID: 15333258]

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Article Details

Year: 2020
Published on: 30 June, 2020
Page: [724 - 729]
Pages: 6
DOI: 10.2174/1573412915666190314123547
Price: $65

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