RESUMO
In the present study, a sensitive LC-MS/MS method was developed and validated to measure pioglitazone (PGZ) concentrations in rat plasma and tissues. The chromatographic separation was achieved by using a YMC Pro C18 column (100 mm × 4.6 mm, 3µ) with a mobile phase consisting of formic acid (0.1% v/v) and acetonitrile (5 : 95) at a flow rate of 0.7 mL min-1 and injection volume of 10 µL (IS: rosiglitazone). Mass spectrometric detection was done using triple quadrupole mass spectrometry using the ESI interface operating in a positive ionization mode. The developed method was validated over a linearity range of 1-500 ng mL-1 with detection and a lower quantification limit of 0.5 ng mL-1 and 1 ng mL-1. The method accuracy ranged from 95.89-98.78% (inter-day) & 93.39-97.68% (intra-day) with a precision range of 6.09-8.12% for inter-day & 7.55-9.87% for intra-day, respectively. The PGZ shows the highest C max of 495.03 ng mL-1 in plasma and the lowest C max, 24.50 ± 2.71 ng mL-1 in bone. The maximum T max of 5.00 ± 0.49 h was observed in bone and a minimum of 1.01 ± 0.05 h in plasma. The AUC(0-24 h and 0-∞) values are highest in plasma (1056.58 ± 65.78 & 1069.38 ± 77.50 ng h-1 mL-1) and lowest in brain (166.93 ± 15.70 &167.12 ± 16.77 ng h-1 mL-1), and the T 1/2 was highest in plasma (5.62 ± 0.74 h) and lowest in kidney (2.78 ± 0.19). The developed method was successfully used to measure the PGZ pharmacokinetic and tissue distribution. Further, the developed method could be utilized for validating target organ (adipose tissue) specific delivery of PGZ (nano-formulations) in addition to conventional dosage forms.