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Fentanyl is a potent analgesic drug in relieving chronic pain in patients. In this report, we present a simple, reliable and sensitive LC-ID/MS method for the quantification of fentanyl in human plasma. LC-ID/MS analysis was carried out on a triple quadrupole mass spectrometer operated in positive electrospray ionization multiple-reaction-monitoring using the transitions m/ z 337.6 → 187.9 for fentanyl and m/ z 342.6 → 187.9 for the internal standard (D5-fentanyl). The calibration curve covered the range 0.02-10 ng/mL. The intra- and inter-batch precision were less than 6.739 and 3.126% for fentanyl and IS, with accuracy from 94.16 to 102.0%. The lower limit of quantification was identifiable and reproducible at 0.02 ng/mL. The validated method offered increased sensitivity and wide linear concentration range. This method was successfully adopted for the evaluation of bioequivalence of two fentanyl transdermal preparations after single dose administration to 20 Chinese pain-patients. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

A simple, reliable and sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) protocol was developed and validated for quantification of bisoprolol in human plasma. The sample was pretreated with a simple procedure of protein precipitation and an isotope-labeled d5-bisoprolol was used as internal standard. The chromatographic separation was performed on a Capcell Pak C18 MG III column (100 mm × 2.0 mm, 5 µm). The protonated ion of the analyte was detected in positive ionization by multiple reaction monitoring mode. The mass transition pairs of m/z 326.3 → 116.3 and m/z 331.3 → 121.3 were used to detect bisoprolol and the internal standard, respectively. Linearity, accuracy, precision, recovery, matrix effect, dilution test and stability were evaluated during method validation over the range of 0.5-100 ng/mL. The validated method was successfully applied to analyze human plasma samples in a bisoprolol bioavailability study. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

A rapid and sensitive liquid chromatography-isotope dilution tandem mass spectrometry method was developed and validated for quantification of itraconazole (ITZ) and its active metabolite hydroxyitraconazole (OH-ITZ ) in human plasma. The plasma samples were extracted with tert-butyl methyl ether and two isotope-labeled internal standards (D5-itraconazole and D5-hydroxyitraconazole) were used. The chromatographic separation was performed on a Capcell Pak C18 MG III (100 × 2 mm, 5 µm, Shiseido). The protonated ions of analytes were detected in positive ionization in multiple reaction monitoring mode. The plasma method has a lower limit of quantification of 1 ng/mL with a linearity range of 1-500 ng/mL for ITZ and OH-ITZ using 100 µL of plasma. The recoveries of the method were found to be 69.47-71.98% for ITZ and 75.68-82.52% for OH-ITZ. The intra- and inter-batch precision was less than 11% for all quality control samples at concentrations of 2.5, 200 and 400 ng/mL. These results indicate that the method was efficient with a short run time (4.5 min) and acceptable accuracy, precision and sensitivity.The validated method was successfully applied to analysis of human plasma samples in pharmacokinetics study. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

A simple, reliable and sensitive liquid chromatography-isotope dilution mass spectrometry (LC-ID/MS) was developed and validated for quantification of olanzapine in human plasma. Plasma samples (50 microL) were extracted with tert-butyl methyl ether and isotope-labeled internal standard (olanzapine-D3) was used. The chromatographic separation was performed on XBridge Shield RP 18 (100 mm x 2.1 mm, 3.5 microm, Waters). An isocratic program was used at a flow rate of 0.4 m x min(-1) with mobile phase consisting of acetonitrile and ammonium buffer (pH 8). The protonated ions of analytes were detected in positive ionization by multiple reactions monitoring (MRM) mode. The plasma method, with a lower limit of quantification (LLOQ) of 0.1 ng x mL(-1), demonstrated good linearity over a range of 0.1 - 30 ng x mL(-1) of olanzapine. Specificity, linearity, accuracy, precision, recovery, matrix effect and stability were evaluated during method validation. The validated method was successfully applied to analyzing human plasma samples in bioavailability study.

This study developed a method for simultaneously assessing the inhibitory potency of compounds on five major cytochrome P-450 ( CYP450) enzymes using a cocktail of probe substrates. A cocktail selective substrates consisting of the phenacetin (PN, CYP1A2), dextromethorphan (DM, CYP2D6), tolbutamide (TB, CYP2C9), omeprazole (OPZ, CYP2C19) and midazolam (MPZ, CYP3A4) was incubated with human liver microsomes. The concentrations of the substrate metabolites paracetamol, dextrorphan, 4-hydroxytolbutamide, 5-hydroxyomeprazole and 1'-hydroxymidazolam were determined by LC/MS/MS in a single assay sample. The method was validated by incubating known CYP inhibitors--alpha-naphthoflavone (ANF, CYP1A2), quinidine (QND, CYP2D6), sulfaphenazole (SUL, CYP2C9), fluconazole (FLU, CYP2C19) and ketoconazole (KET, CYP3A4) with the individual substrates and with the substrate cocktail. The IC50 values were then determined. The IC50s (micromol x L(-1)) were in good agreement with those obtained with individual substrates (alpha-naphthoflavone, 0.18 vs 0.26; quinidine, 0.058 5 vs 0.058 4; sulfaphenazole, 0.48 vs 0.45; fluconazol, 17.5 vs 11.4; ketoconazole, 0.22 vs 0.24) and with previously reported values in the literature. This cocktail probe substrate method can be utilized for the rapid simultaneous determination of the inhibition potential of compounds on the five CYP450 enzymes.