Advion. (8/11/11). "Press Release: Advion Devloping H4 Method for Clopidogrel and the Inactive Metabolites". Ithaca, NY.

	Organisation	Advion BioServices Inc.
	Group	Quintiles (Group)
	Product	mass spectrometry solution/method
	Person	Boardman, Amy (Advion 200708 MarCom Manager)

Clopidogrel is an inactive prodrug that is metabolized stepwise to its pharmacologically active metabolite (clopidogrel active metabolite; CAM) by cytochrome P450 enzymes. CAM is unstable in whole blood and plasma and requires derivatization upon collection, usually by using 2-Bromo-3'-methoxyacetophenone (BMAP). This procedure has been well documented in the literature (1). Many bioanalytical methods have historically measured plasma concentrations of clopidogrel and its inactive carboxylic acid metabolite as surrogates for plasma levels of CAM due to the difficulty of developing methods specific for CAM. Since the structure of CAM has been shown exist in the Z configuration any reference standard employed for bioanalysis would also be required to incorporate this orientation. However, due to the difficulty of synthesizing the less favored Z diastereomer, many bioanalytical methods have employed the more readily available E diastereomer. CAM has also been shown be only one of a pair of Z diastereomers (H4) while the corresponding Z diastereomer H3 has been shown to have little activity (2, 3). Therefore, existing methods that merge H3 and H4 (1) into a single chromatographic peak are less desirable than those that separate H3 and H4 (3). This is especially true in studies attempting to evaluate drug-drug interactions (4). Advion has recently validated a method specific for H4 and this method has been used in clinical analysis of thousands of samples. This method will be redeveloped to include clopidogrel and the inactive metabolite as well in the near future.

A full list of Advion's validated LC/MS and immunoassay methods to support drug-drug interactions or comparative studies is available on its website.

REFERENCES

1. Quantitative determination of clopidogrel active metabolite in human plasma by LC-MS/MS. Takahashi, M.; Pang, H.; Kawabata, K.; et al. J. Pharm. Biomed. Anal. 2008 48:1219-1224.
2. Structure and sterochemistry of the active metabolite of clopidogrel. Pereillo, J.-M.; Maftouh, M.; Andrieu, A.; et al. Drug Metab. Dispos. 2002 30:1288-1295.
3. An improved method for specific and quantitative determination of the clopidogrel active metabolite isomers in human plasma. Tuffal, G.; Roy, S.; Lavisse, M.; et al. Thromb. Haemostasis 2011 105.5:696-705.
4. Differential Effects of Omeprazole and Pantoprazole on the Pharmacodynamics and Pharmacokinetics of Clopidogrel in Healthy Subjects: Randomized, Placebo-Controlled, Crossover Comparison Studies. Angiolillo, D.J.; Gibson, C.M.; Cheng, S.; et al.Clin. Pharmacol. Ther. 2011 89:65-74.

About Advion BioServices, Inc.

Advion is a scientific leader in bioanalytical and immunoassay services. Advion offers a range of GLP-compliant and discovery support services including bioanalytical LC/MS/MS, LC/MS biomarker analysis, immunoassay, dose formulation analysis, P450 inhibition study support, sample management, and sample storage. The company is the laboratory of choice for pharmaceutical and biotechnology companies in pursuit of scientific excellence.

More information about the company can be found on its website www.advion.com .

For Advion:

Amy Boardman
Manager of Corporate Marketing Communications
1.607.266.0665
aboardman@advion.com

Record changed: 2011-11-25

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Advion. (8/11/11). "Press Release: Advion Devloping H4 Method for Clopidogrel and the Inactive Metabolites". Ithaca, NY.

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