Lanzhou University, People's Republic of China.
Anal Biochem. 2011 Jan 1;408(1):147-56. doi: 10.1016/j.ab.2010.09.015. Epub 2010 Sep 17.
A quantitative analysis of a recalled contaminated lot of heparin sodium injection U.S. Pharmacopeia (USP) was undertaken in response to the controversy regarding the exact nature of the contaminant involved in the heparin (HP) crisis. A mass balance analysis of the formulated drug product was performed. After freeze-drying, a 1-ml vial for injection afforded 54.8±0.3 mg of dry solids. The excipients, sodium chloride and residual benzyl alcohol, accounted for 11.4±0.5 and 0.9±0.5 mg, respectively. Active pharmaceutical ingredient (API) represented 41.5±1.0 mg, corresponding to 75.7 wt% of dry mass. Exhaustive treatment of API with specific enzymes, heparin lyases, and/or chondroitin lyases was used to close mass balance. HP represented 30.5±0.5 mg, corresponding to 73.5 wt% of the API. Dermatan sulfate (DS) impurity represented 1.7±0.3 mg, corresponding to 4.1 wt% of API. Contaminant, representing 9.3±0.1 mg corresponding to 22.4 wt% of API, was found in the contaminated formulated drug product. The recovery of contaminant was close to quantitative (95.6-100 wt%). A single contaminant was unambiguously identified as oversulfated chondroitin sulfate (OSCS).
为了回应肝素（HP）危机中涉及的污染物的确切性质的争议，对召回的肝素钠注射液美国药典（USP）污染批次进行了定量分析。对制剂药物进行了质量平衡分析。冷冻干燥后，每个 1 毫升的注射小瓶可提供 54.8±0.3 毫克的干燥固体。赋形剂氯化钠和残留的苯甲醇分别占 11.4±0.5 和 0.9±0.5 毫克。活性药物成分（API）占 41.5±1.0 毫克，相当于干燥质量的 75.7wt%。使用特定的酶、肝素酶和/或软骨素酶对 API 进行彻底处理以封闭质量平衡。HP 代表 30.5±0.5 毫克，相当于 API 的 73.5wt%。硫酸皮肤素（DS）杂质代表 1.7±0.3 毫克，相当于 API 的 4.1wt%。在污染的制剂药物中发现了 9.3±0.1 毫克的污染物，相当于 API 的 22.4wt%。污染物的回收率接近定量（95.6-100wt%）。一种单一的污染物被明确鉴定为过硫酸化软骨素硫酸盐（OSCS）。
