Medical Liaison Office, Merck Serono S.p.A., Roma, Italy.
J Pharm Sci. 2009 Dec;98(12):4511-24. doi: 10.1002/jps.21774.
The objective of the present study was to assess (I) the potential presence of a recently discovered thioether variant in commercially available recombinant human growth hormone (r-hGH) preparations, and (II) the impact of the thioether modification on the in-vivo bioactivity and the receptor binding kinetics. Samples were tested employing European (EP) and US Pharmacopeia (USP) Somatropin monograph and mass spectrometry methods. None of the international standards contained this variant. All products conformed to EP specifications but six out of eight lots contained the variant. An artificially enriched thioether sample exhibited a significantly reduced in vivo biopotency and altered receptor-binding properties compared with a control. The absence of the variant in the pituitary hGH standard, and the possibility to generate it artificially suggests that it is not naturally occurring and that it may arise from an uncontrolled manufacturing process. Controlled studies may be required to assess its clinical efficacy and safety. EP and USP methods may need to be adapted to reliably detect the presence of the variant.
(I) 市售重组人生长激素(r-hGH)制剂中是否存在最近发现的硫醚变体，以及 (II) 硫醚修饰对体内生物活性和受体结合动力学的影响。采用欧洲药典(EP)和美国药典(USP)生长激素专论和质谱法对样品进行了测试。国际标准品中均未包含该变体。所有产品均符合 EP 规格，但 8 批产品中有 6 批含有该变体。与对照品相比，人工富集的硫醚样品表现出明显降低的体内生物效价和改变的受体结合特性。该变体在垂体 hGH 标准品中不存在，并且可以人工生成，这表明它不是天然存在的，可能是由于制造过程失控所致。可能需要进行对照研究以评估其临床疗效和安全性。EP 和 USP 方法可能需要进行调整以可靠地检测变体的存在。
