Simplified method for determination of rosiglitazone in human plasma.

Rosiglitazone is a thiazolidinedione antihyperglycemic drug used in the treatment of type 2 diabetes mellitus. Rosiglitazone is extensively metabolized by cytochrome P450 2C8 and so may have some utility as an in vivo probe for this enzyme. A liquid chromatographic method using sensitive fluorescence detection and simplified sample processing involving protein precipitation with acetonitrile was developed. The isocratic mobile phase consisted of 10 mM sodium acetate-acetonitrile (pH 5; 60:40, v/v) and was delivered at a flow rate of 1 ml/min to an Alltima phenyl column (250 mm x 4.6 mm, 5 microm). Detection was by fluorescence at (EX/EM) 247/367 for rosiglitazone and 235/310 for the internal standard betaxolol. Intra- and inter-day precision ranged from 3.1 to 8.5% and 2.3 to 5.7%, respectively. No endogenous interference was observed with either rosiglitazone or the internal standard. The assay is simple, economical, precise, and is directly applicable to human pharmacokinetic studies involving single dose rosiglitazone administration.