“…The C max and AUC of OPZ are approximately proportional in doses up to 40 mg, but because of a saturable first-pass effect, a greater than linear response in C max and AUC occurs with doses greater than 40 mg. Absolute bioavailability (compared with intravenous administration) is about 30-40% at doses of 20-40 mg, due in large part to pre-systemic metabolism (Andersson, 1996). Several LC-MS/MS bioanalytical methods have been reported for estimation of OPZ alone or along with its metabolites in human biological samples (Woolf and Matuszewski, 1998;Stenhoff et al, 1999;Kanazawa et al, 2002;Yin et al, 2004;Frerichs et al, 2005;Wang et al, 2005;Hofmann et al, 2006;Song and Naidong, 2006;Hultman et al, 2007;Martens-Lobenhoffer et al, 2007). Although the reported LC-MS/MS methods are sensitive enough, the reported lowest limit of quantitation (LLOQ) amongst them was 0.4 ng/mL (Frerichs et al, 2005).…”