DETERMINATION OF PACLITAXEL BY 3D VIEW LC-DIODE ARRAY UV: ITS APPLICATION TO AN IN SITU CLOSED LOOP RE-CIRCULATING INTESTINE ABSORPTION STUDY IN RATS

Abstract

Paclitaxel (TAX) amount remaining to be absorbed from the intestine in the in situ closed loop, re-circulating absorption samples were estimated by the 3D view LC-diode array method. The Log ARA versus time graph (r²) of TAX loaded nanoparticles (NP)s explains that there is exponential disappearance of TAX from the intestine, which indicates TAX NPs follows first order absorption kinetic. The calculated K_a and t_1/2 of TAX and TAX loaded NPs were 0.9, 1.02, 1.38, and 1.74/min and 46.20, 40.66, 30.09, and 23.88 min, respectively, shows the rapid absorption of TAX NPs from the intestine than the pure drug TAX. The 3D view chromatogram, counter view graph, UV, and IR spectrum of the degradation samples confirms the selectivity and specificity of the developed method. The peak purity curve of all the samples shows that the similarity curve did not intersect the threshold curve and the rectangular ratiograms, in addition, demonstrates the selectivity and specificity nature of the 3D view LC-method. The accuracy of the developed methods was tested by placebo spiking and standard addition method. The LOD and LLOQ of the methods 0.39 µg mL,⁻¹ 1.18 µg mL⁻¹ and 2.96 ng mL,⁻¹ 8.96 ng mL⁻¹ respectively.

Keywords:

• 3D chromatogram
• closed loop re-circulating absorption
• counter view plot
• paclitaxel
• purity curve
• ratiogram

ACKNOWLEDGMENT

Author Sekar Vasanthakumar acknowledges the Council of Scientific and Industrial Research (CSIR- India) for providing the Senior Research Fellowship (SRF). The authors are also thankful to Getwell Pharmaceuticals, India, for the generous gift samples of Paclitaxel.

Notes

PEG-Polyethylene glycol, MPEG-methoxy polyethylene glycol, MP-microparticle.

^a Standard error of mean.

^b Calculated at p = 0.05 level of significance, using the test of the intercept (t _df  = | C – α | / Ś_c).

^c Calculated based on one-way ANOVA test at P = 0.05 level of significance.

^d Calculated at P = 0.05 level of significance (d.f. 2) based on paired t-test.

^e Standard error of mean.

^f Calculated at p = 0.05 level of significance, using the test of the intercept (t _df  = | C – α | / Ś_c).

^g Calculated based on one-way ANOVA test at P = 0.05 level of significance.

^h Calculated at P = 0.05 level of significance (d.f. 4) based on paired t-test, A-Based on the formula 3.3 σs⁻¹, B-Based on the formula 10 σs⁻¹, where σ- standard deviation of intercept and s- slope of the calibration curve.