The purpose of this study is to compare the bioavailability of two itraconazole (CAS 84625-61-6) capsule formulations. An open, randomized, two-period crossover study with a 7-day washout interval was conduced in 32 healthy volunteers. The plasma samples were obtained up to 96 h after drug administration. A sensitive and specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the determination of itraconazole in human plasma. Itraconazole and ketoconazole (internal standard) were extracted from the plasma by liquid-liquid extraction using diethylether : dichloromethane (70 : 30) as extraction solvent and separated on a C8 analytical column (150 mm x 4.6 mm I.D.) maintained at 40 degrees C. The elution was performed by a constant flow rate of 1.2 mL/min and the mobile phase consisted of acetonitrile and acetic acid 0.1% (85 :15 v/v). The mass spectrometer equipped with an electrospray source in positive mode, was set up in multiple reaction monitoring, to detect parent --> production 705.0 392.0 (itraconazole) and 531.0 --> 81.70 (ketoconazole). The chromatographic separation was obtained within 3.5 min and was linear in the concentration range of 5 to 600 ng/mL. Bioequivalence between the products was determined by calculating 90% confidence intervals for the ratio of C(max) (95.02%-109.48%), AUC(0-t) (81.41%-107.77%) and AUC(0-inf) (80.85%-106.86%). These values for the test and reference products are within the 80-125% interval, proposed by FDA and EMEA. It was concluded that the proposed method was successfully applied to a pharmacokinetic study in healthy human volunteers, and results showed that the two itraconazole formulations are bioequivalent in their rate and extent of absorption.
An analytical method based on reversed phase liquid chromatography (RP-LC) was developed and validated for the determination of acyclovir in human plasma. Acyclovir and guanine (internal standard) were extracted from the plasma by liquid-liquid extraction using acidified acetonitrile as extraction solvent, and separated on a C 18 analytical column (150'mm  4.6 mm I.D.) maintained at 308C. The elution was performed by a fast gradient at a constant flow rate of 1.0 mL/min and the mobile phase A consisted of 1% formic acid, and mobile phase B consisted of acetonitrile. The fluorescence detector was set at 270 nm (excitation) and 380 nm (emission). The chromatographic separation was obtained within 16.0 min and was linear in the concentration range of 20 -3000 ng/mL. The mean extraction recoveries of acyclovir and guanine from plasma were 82.2 and 76.0%, respectively. Method validation investigated parameters such as the specificity, linearity, precision, accuracy, and stability, giving results within the acceptable range. Moreover, the proposed method was successfully applied to a pharmacokinetic study in healthy human volunteers, and results showed that the two acyclovir formulations are bioequivalent in their rate and extent of absorption.
A fast, sensitive, and specific liquid chromatographic/tandem mass spectrometric method was developed and validated for determination of tetracycline in human plasma. Tetracycline and oxytetracycline [internal standard (IS)] were extracted from the plasma by protein precipitation. The mobile phase consisted of acetonitrileformic acid 0.1 (48 + 52, v/v), run at a flow rate of 1 mL/min (split 1:5). Detection was performed by positive electrospray ionization in multiple reaction monitoring mode, monitoring the transitions 444.8 > 410.0 and 461.0 > 426.0 for tetracycline and IS, respectively. The analysis was performed in 3.5 min and the method was linear in the plasma concentration range of 506000 ng/mL. The mean extraction recoveries for tetracycline and IS from plasma were 92.14 and 94.04, respectively. Method validation investigated parameters such as the linearity, precision, accuracy, specificity, and stability, giving results within the acceptable range. The proposed method was successfully applied for determination of tetracycline in human plasma samples to support bioequivalence studies.
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