A Collaborative Study of Proposed European Pharmacopoeia Reference Preparations of Low Molecular Mass Heparin

1995 ◽  
Vol 74 (03) ◽  
pp. 893-899 ◽  
Author(s):  
E Gray ◽  
A B Heath ◽  
B Mulloy ◽  
J-M Spiese ◽  
T W Barrowcliffe
Keyword(s):  
Molecular Mass ◽  
Low Molecular Weight Heparin ◽  
Collaborative Study ◽  
Low Molecular Weight ◽  
European Pharmacopoeia ◽  
Response Curves ◽  
Working Standard ◽  
Assay Methods ◽  
European Collaborative Study ◽  
Working Standards

SummaryA European collaborative study, in which 16 laboratories participated, was carried out to assess the performance of the European Pharmacopoeia (EP) monograph methods for anticoagulant activities (anti-Xa and anti-IIa assays) of low molecular mass (EMM) heparin and to assess the suitability of six candidate materials as the EP working standard for LMM heparin. There was good interlaboratory agreement for both types of assays as indicated by most gcv’s being less than 10%, indicating acceptable performance of the EP assay methods. All the candidate preparations gave dose-response curves parallel to the 1st International Standard for Low Molecular Weight heparin and to each other. All preparations, possibly with the exception of E and F, gave similar performance as measured by interlaboratory agreement and would be suitable as working standards. Based on these data, preparations A, B, C and D have been established by the EP as official EP Biological Reference Preparations and they will be issued as successive batches.

An International Standard for Low Molecular Weight Heparin

1988 ◽  
Vol 60 (01) ◽  
pp. 001-007 ◽  
Author(s):  
T W Barrowcliffe ◽  
A D Curtis ◽  
E A Johnson ◽  
D P Thomas
Keyword(s):  
Molecular Weight ◽  
Low Molecular Weight Heparin ◽  
Collaborative Study ◽  
Low Molecular Weight ◽  
International Standard ◽  
Thrombin Inhibition ◽  
Interlaboratory Variability ◽  
Assay Methods ◽  
The Mean ◽  
International Collaborative Study

SummaryAn international collaborative study has been carried out with the aim of establishing an international standard for low molecular weight (LMW) heparin. Three preparations of LMW heparin were assayed against the International Standard for unfractionated heparin (UFH) by 25 laboratories in 13 countries, using nine different assay methods. The results confirmed previous findings of non-parallel assays, wide interlaboratory variability and differences between methods when LMW heparins are assayed against a UFH standard. Use of one of the LMW heparins as a standard for the other two gave parallel assays and much closer agreement between laboratories. The preparation in ampoules coded 85/600 was selected as likely to give the best agreement with the largest number of LMW heparins; potencies were assigned by taking the mean of all the anti-Xa assays, and the mean of the thrombin and APTT assays, to represent the two major groups of activities. Preparation 85/600 has been established by WHO as the 1st International Standard for LMW heparin, with potencies of 1,680 iu/ampoule by anti-Xa assays and 665 iu/ampoule by thrombin inhibition and APTT assays.

THE FIRST INTERNATIONAL STANDARD FOR HUMAN URINARY FSH AND FOR HUMAN URINARY LH (ICSH), FOR BIOASSAY

1976 ◽  
Vol 83 (4) ◽  
pp. 700-710 ◽  
Author(s):  
P. L. Storring ◽  
H. Dixon ◽  
D. R. Bangham
Keyword(s):  
Elevated Temperatures ◽  
Collaborative Study ◽  
Storage Conditions ◽  
Working Standard ◽  
International Standard ◽  
Accelerated Degradation ◽  
Reference Preparation ◽  
Degradation Studies ◽  
The Stability ◽  
Working Standards

ABSTRACT This paper describes the preparation and nature of the First International Standard for Human Urinary Follicle Stimulating Hormone and for Human Urinary Luteinizing Hormone, for Bioassay, and of two batches of working standard which were prepared from the same material. A collaborative study of these materials was carried out by six laboratories in six different countries. The FSH and LH activities of the Standard were assayed in terms of those of the Second International Reference Preparation of Human Menopausal Gonadotrophins, Urinary, for Bioassay, which it replaces. The results from 20 valid FSH assays and 30 valid LH assays (using four different methods) obtained in this way gave a weighted combined potency estimate for FSH of 53.7 IU, with 95 fiducial limits of 47.2–61.1 IU, and for LH of 46.2 IU, with 95% fiducial limits of 43.3–49.3 IU. Accelerated degradation studies of the Standard stored at elevated temperatures suggested that the stability of both FSH and LH activities under normal storage conditions would be satisfactory. The FSH and LH activities of the two batches of working standard (WS-A and WS-B) were compared with those of the Standard and were not found to differ significantly, except for the LH activity of WS-B which appeared to be slightly higher than that of the Standard. Accelerated degradation studies did not show any significant differences in stability between the Standard and batches of working standards. On the basis of these results the Standard has been established by WHO and allocated a potency for FSH of 54 IU per ampoule and for LH 46 IU per ampoule. The International Units for FSH, Human Urinary, for Bioassay and for LH (ICSH), Human Urinary, for Bioassay are thus defined as the activities contained in 0.11388 mg and 0.13369 mg of the International Standard, respectively.

Standardization of Low Molecular Weight Heparins : A Collaborative Study

1985 ◽  
Vol 54 (03) ◽  
pp. 675-679 ◽  
Author(s):  
T W Barrowcliffe ◽  
A D Curtis ◽  
T P Tomlinson ◽  
A R Hubbard ◽  
E A Johnson ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Collaborative Study ◽  
Assay Method ◽  
Low Molecular Weight ◽  
Low Molecular Weight Heparins ◽  
International Standard ◽  
Assay Methods

SummaryA collaborative study was carried out, in which eight laboratories each assayed eight low molecular weight (LMW) heparins against the International Standard (IS) for heparin. APTT assays and three types of anti-Xa method were used. The results of this study showed that:1. LMW heparins cannot be validly assayed against the IS by APTT or anti-Xa methods.2. Potencies of LMW heparins vs. the IS differed considerably between the four types of assay method used and also between different laboratories using the same type of method.3. Adoption of a single LMW heparin standard would improve validity, improve inter-laboratory variation, and largely abolish the differences between the three types of anti-Xa method. However, since calibration of a LMW heparin standard against the IS would give potencies that differ widely by the different assay methods, a single assay method such as the anti-Xa amidolytic, plasma, would need to be chosen for this calibration.

Measurement of Low Molecular Weight Heparin Ex Vivo Activities in Clinical Laboratories Using Various Anti-Xa Assays: Interlaboratory Variability and Requirement for an Agreed Low Molecular Weight Heparin Standard

1987 ◽  
Vol 58 (03) ◽  
pp. 879-883 ◽  
Author(s):  
P Sié ◽  
M F Aillaud ◽  
D de Prost ◽  
C Droullé ◽  
F Forestier ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Low Molecular Weight Heparin ◽  
Ex Vivo ◽  
Collaborative Study ◽  
Factor Xa ◽  
Low Molecular Weight ◽  
Low Molecular Weight Heparins ◽  
Clinical Laboratories ◽  
Interlaboratory Variability ◽  
Factor Xa Inhibition

SummaryThe only sensitive and convenient assay to assess the biological activity of low molecular weight heparins (LMWHs) is based on the potentiation of activated factor Xa inhibition. Several procedures for measuring the socalled anti Xa activity have been proposed. In this collaborative study including eight laboratories, we have used four different assays (three amidolytic and one clotting based methods) for measuring the anti Xa activity of ex vivo samples obtained after injecting three different LMWHs. The dispersion of the results obtained by calibration against standard heparin could be reduced by using any of the three LMWHs for calibration. A coefficient of variation less than 0.20 between values obtained in different laboratories using a variety of methods seems acceptable. However it is necessary to refer to a common international standard for expressing the results in units and to define, for each of the three products, the therapeutic range.

Low-molecular-weight heparin in the prevention and treatment of thromboembolic disorders

1998 ◽  
Vol 1 (5) ◽  
pp. 166-174 ◽  
Author(s):  
Evelyn R Hermes De Santis ◽  
Betsy S Laumeister ◽  
Vidhu Bansal ◽  
Vandana Kataria ◽  
Preeti Loomba ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Low Molecular Weight Heparin ◽  
Low Molecular Weight ◽  
Prevention And Treatment

Effects of Low Molecular Weight Heparin and Unfragmented Heparin on Induction of Osteoporosis in Rats

1990 ◽  
Vol 63 (03) ◽  
pp. 505-509 ◽  
Author(s):  
Thomas Mätzsch ◽  
David Bergqvist ◽  
Ulla Hedner ◽  
Bo Nilsson ◽  
Per Østergaar
Keyword(s):  
Molecular Weight ◽  
Bone Mineral ◽  
Low Molecular Weight Heparin ◽  
Zinc Content ◽  
Low Molecular Weight ◽  
Dependent Manner ◽  
Bone Mineral Mass ◽  
Bone Ash ◽  
Dose Dependent ◽  
Mineral Mass

SummaryA comparison between the effect of low molecular weight heparin (LMWH) and unfragmented heparin (UH) on induction of osteoporosis was made in 60 rats treated with either UH (2 IU/ g b w), LMWH in 2 doses (2 Xal U/g or 0.4 Xal U/g) or placebo (saline) for 34 days. Studied variables were: bone mineral mass in femora; fragility of humera; zinc and calcium levels in serum and bone ash and albumin in plasma. A significant reduction in bone mineral mass was found in all heparin-treated rats. There was no difference between UH and LMWH in this respect. The effect was dose-dependent in LMWH-treated animals. The zinc contents in bone ash were decreased in all heparin-treated rats as compared with controls. No recognizable pattern was seen in alterations of zinc or calcium in serum. The fragility of the humera, tested as breaking strength did not differ between treatment groups and controls. In conclusion, if dosed according to similar factor Xa inhibitory activities, LMWH induces osteoporosis to the same extent as UH and in a dose-dependent manner. The zinc content in bone ash was decreased after heparin treatment, irrespective of type of heparin given.

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