The establishment and validation of efficient assays for anti-IIa and anti-Xa activities of heparin sodium and heparin calcium

被引：17

作者：

Suzuki, Takuo ^{[1
]}

Ishii-Watabe, Akiko ^{[1
]}

Hashii, Noritaka ^{[1
]}

Nakagawa, Yukari ^{[2
]}

Takahashi, Tomoko ^{[2
]}

Ebisawa, Akiko ^{[2
]}

Nishi, Seiichi ^{[3
]}

Fujita, Naho ^{[3
]}

Bando, Aya ^{[4
]}

Sekimoto, Yuko ^{[4
]}

Miyata, Kazuyoshi ^{[4
]}

Endo, Toshio ^{[5
]}

Otsu, Takuma ^{[5
]}

Sugimoto, Shiori ^{[6
]}

Kondou, Tadashi ^{[6
]}

Fujita, Yuji ^{[7
]}

Miyanaga, Naoyuki ^{[8
]}

Mashimo, Masahiro ^{[8
]}

Shimada, Norihiko ^{[8
]}

Yoden, Hikaru ^{[9
]}

Shimamura, Hideo ^{[9
]}

Kurata, Yasunori ^{[9
]}

Koyama, Sadatoshi ^{[10
]}

Kawasaki, Nana ^{[1
]}

机构：

[1] Natl Inst Hlth Sci, Tokyo 1588501, Japan

[2] Pharmaceut & Med Device Regulatory Sci Soc Japan, Tokyo, Japan

[3] Ajinomoto Pharmaceut Co Ltd, Tokyo, Japan

[4] Otsuka Pharmaceut Factory Inc, Naruto, Japan

[5] Sawai Pharmaceut Co Ltd, Tokyo, Japan

[6] Teva Pharrna Japan Inc, Takayama, Gifu, Japan

[7] Terumo Co Ltd, Tokyo, Japan

[8] Nipro Pharma Corp, Osaka, Japan

[9] Fuso Pharmaceut Ind Ltd, Osaka, Japan

[10] Mochida Pharmaceut Plant Co Ltd, Otawara, Tochigi, Japan

来源：

BIOLOGICALS | 2013年 / 41卷 / 06期

关键词：

Heparin; Anti-IIa assay; Anti-Xa assay; Quality control; COFACTOR ASSAY; ANTITHROMBIN;

D O I：

10.1016/j.biologicals.2013.09.003

中图分类号：

Q5 [生物化学];

学科分类号：

070307 [化学生物学];

摘要：

Heparin is used as an anticoagulant drug. The anticoagulation process is mainly caused by the interaction of heparin with antithrombin followed by inhibition of anticoagulant factor IIa and factor Xa. The anti-factor Ha and anti-factor Xa activities of heparin are critical for its anticoagulant effect; however, physicochemical methods that can reflect these activities have not been established. Thus, the measurements of anti-IIa and anti-Xa activities by biological assay are critical for the quality control of heparin products. Currently in the Japanese Pharmacopoeia UP), the activities of heparin sodium and heparin calcium are measured by an anti-Xa activity assay (anti-Xa assay), but anti-IIa activity is not measured. Here, we established an anti-IIa activity assay (anti-IIa assay) and an anti-Xa assay having good accuracy and precision. When samples having a relative activity of 0.8, 1.0 and 1.2 were measured by the established anti-IIa and anti-Xa assays in nine laboratories, good accuracy (100.0-102.8% and 101.6-102.8%, respectively), good intermediate precision (1.9-2.1% and 2.4-4.2%, respectively) and good reproducibility (4.0-4.8% and 3.6-6.4%, respectively) were obtained. The established anti-IIa and anti-Xa assays have similar protocols, and could be performed by a single person without a special machine. The established assays would be useful for quality control of heparin. (C) 2013 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

引用

页码：415 / 423

页数：9

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