Analytical Study of the Antifungal Posaconazole in Raw Material: Quantitative Bioassay, Decomposition Chemical Kinetics, and Degradation Impurities by LC-QTOF-MS

Abstract

Background Posaconazole is a triazole antifungal drug approved by FDA in 2006. No bioassay is available in literature or official codes for potency determination in bulk. Objective To conduct an analytical study focused on posaconazole in bulk. Methods An alternative microbiological assay was validated for drug quantitation, applying agar diffusion technics (3 x 3 design), using Saccharomyces cerevisiae ATCC MYA 1942 as test microorganism (2% inoculum). An isocratic HPLC-DAD method, with C8 Shim-pack column (250 x 4.6 mm, 5 μm) and methanol:water (75:25 v/v) mobile phase was used for stress stability by photolysis and oxidation, indicating the formation of degradation products, which were investigated by UPLC-QTOF-MS. Results The established conditions for the bioassay were satisfactory. It was linear in the range evaluated (2.5 – 10.0 µg/mL), as well as precise, accurate and robust. Stress tests showed drug susceptibility to the factors evaluated (60 % of degradation after 120 min). Kinetics curves for photolytic decomposition followed first-order. From photolytic and oxidative degraded matrix, three major degradation products were identified as being derivatives with modifications in the piperazine central ring and in the triazole and triazolone side chains, whose mass spectra results were m/z 683 (DP1), m/z 411 (DP2), m/z 465 (DP3). Conclusions Microbiological method was adequately validated and demonstrated to be equivalent to physico-chemical ones. Impurities found are described for the first time in studies with posaconazole raw material. Highlights a microbiological bioassay was developed for posaconazole; first-order kinetics was determined for photolytic degradation; structures for new degradation products were suggested.

Advancing posaconazole quantification analysis with a new reverse-phase HPLC method in its bulk and marketed dosage form

“…This study aims to develop and validate a new HPLC analytical method that is quick, sensitive, robust, cheap, and reliable for estimating posaconazole in bulk and dosage form. 11 – 23 …”

“…This study aims to develop and validate a new HPLC analytical method that is quick, sensitive, robust, cheap, and reliable for estimating posaconazole in bulk and dosage form. [11][12][13][14][15][16][17][18][19][20][21][22][23] The HPLC method involves, ▪ Preparing a solution of the active ingredient from the dosage form, ▪ Injecting it into the HPLC system, and ▪ Separating the different components based on their interactions with the stationary phase.…”

Advancing posaconazole quantification analysis with a new reverse-phase HPLC method in its bulk and marketed dosage form

“…This study aims to develop and validate a new HPLC analytical method that is quick, sensitive, robust, cheap, and reliable for estimating posaconazole in bulk and dosage form. [11][12][13][14][15][16][17][18][19][20][21][22][23] The HPLC method involves, ▪ Preparing a solution of the active ingredient from the dosage form, ▪ Injecting it into the HPLC system, and ▪ Separating the different components based on their interactions with the stationary phase.…”