Quantitation of tadalafil in human plasma using a sensitive and rapid LC-MS/MS method for a bioequivalence study

Abstract

A highly sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the determination of tadalafil (TAD) in human plasma. TAD and its deuterated internal standard (IS), tadalafil-d3, were extracted from 200 µL plasma using Phenomenex Strata-X-C 33 µ extraction cartridges. Chromatographic analysis was carried out on Synergi™ Hydro-RP C18 (100 mm × 4.6 mm, 4 µm) column with a mobile phase consisting of methanol and 10 mM ammonium formate, pH 4.0 (90:10, v/v), delivered at a flow rate of 0.9 mL/min. Quantitation of the protonated analyte was done on a triple quadrupole mass spectrometer using multiple reaction monitoring via electrospray ionization. The precursor to product ions transitions monitored for TAD and TAD-d3 were m/z 390.3 → 268.2 and m/z 393.1 → 271.2, respectively. The calibration curve was linear over the concentration range of 0.50–500 ng/mL with correlation coefficient, r2 ≥ 0.9994. Acceptable intra-batch and inter-batch precision (≤ 3.7%) and accuracy (97.8% to 104.1%) were obtained at five concentration levels. The recovery of TAD from spiked plasma was highly precise and quantitative (98.95% to 100.61%). Further, the effect of endogenous matrix components was minimal. TAD was found to be stable under different storage conditions in human plasma and also in whole blood samples. The validated method was successfully used to determine TAD plasma concentration in a bioequivalence study with 20 mg TAD tablets in 24 healthy volunteers. Method performance was evaluated by reanalyzing 115 study samples.

Validated LC-MS/MS method for the determination of Tadalafil – a competitive phosphodiesterase 5 inhibitor (pde5) – from human plasma

“…The calibration curve range is established according to literature data about plasma concentrations of the analyte. C max average from literature for Tadalafil was found to be ~ 450-500 ng/ml, after administration of a 20 mg dose [2][3][4]8].…”

“…There are various methods known in the literature for the determination of tadalafil in human blood, plasma or urine [3,4,[7][8][9], animal plasma [5] or pharmaceutical formulations/dietary supplements [11], using LC-MS/MS methods.…”

A concise review of bioanalytical methods of small molecule immuno‐oncology drugs in cancer therapy

“…The ISNME (internal standard normalized matrix effect) for tadalafil was minimal and was in the range of 98.9-101% across the tested quality control (QC) levels. Chromatographic separation was achieved using a Synergi™ Hydro-RP C 18 column and an isocratic mobile phase was consisting of methanol and 10 mM ammonium formate at pH 4.0 (90:10, v/v) delivered at a flow rate of 0.9 ml/min (Bhadoriya, Dasandi, Parmar, Shah, & Shrivastav, 2018). Kertys, Urbanova, and Mokry (2018) water, which was delivered at a flow rate 0.5 ml/min (Kertys, Urbanova, & Mokry, 2018).…”

Simple bioanalytical method development and validation of micronised Domperidone 20 mg tablets using LCMS-MS and its pharmacokinetic application in Healthy Indian Volunteers

“…The important tuning parameters were calculated and optimized by injecting 100 ng mL -1 of standard solution containing all two drugs including internal standard. The validation parameters like sensitivity, accuracy, precision, stability, recovery, reproducibility and system suitability were measured in accordance with the US-FDA bioanalytical method guidelines (Bhadoriya et al, 2018).…”

“…Bioequivalent study of water insoluble drug has been executed by several researchers but very few related to micronised formulation has been addressed in a proper scientific way. Thorough literature survey finds that several methods was performed for conducting bioequivalent study but an attempt was made here to perform bioequivalent study of micronised domperidoene formulation as compare to conventional domperidone dosage form (Toyama et al, 2015;Bhadoriya et al, 2018;Blandizzi et al, 2015;Censi et al, 2015;Benet, 2013;Rockville, 2001). The interesting research conclusion which may come out from this study can be described as whether micronised drugs formulated as sustained release matrix tablet dosage form are able to deliver better and sustained bioavailability.…”