Validated UPLC-MS/MS method for the determination of tadalafil in human plasma and its application to a pharmacokinetic study

Abstract

A simple, rapid, and reliable UPLC-MS/MS method was developed and validated for the determination of tadalafil in human plasma. The plasma samples were deproteinized with acetonitrile. Chromatographic separation was performed on a Shiseido C18 (100 × 2.1 mm, 2.7 μm) column with isocratic elution using 2.0 mM ammonium acetate and acetonitrile (55:45, v/v) with 0.1% formic acid at a flow rate of 0.7 mL/min. The total run time was 1 min per sample. The quantitative analysis was performed using multiple reaction monitoring at transition of m/z 390.4 → 268.3 for tadalafil and m/z 475.3 → 283.3 for sildenafil as an internal standard. The method was fully validated over a concentration range of 5-1,000 ng/mL with a lower quantification limit of 5 ng/mL. Intra-and inter-day precision (relative standard deviation, %RSD) were within 8.4% and accuracy (relative error, %RE) was lower than -3.2%. The developed and validated method was successfully applied to a pharmacokinetic study of tadalafil (20 mg) in Korean healthy male subjects (n = 12).

Phosphodiesterase 5 inhibition improves contractile function and restores transverse tubule loss and catecholamine responsiveness in heart failure

“…Tadalafil concentrations were subsequently determined using a liquid chromatography-mass spectrometry method modified from Kim et al . 80 . Briefly, following metabolite extraction samples were spiked with heavy stable-isotope containing Tadalafil and Sildenafil (Toronto Research Chemicals, Canada).…”

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

“…The chromatographic separation was done on a Kinetex C 18 column using a gradient elution consisting of 5 mM ammonium acetate acidified with 0.1% acetic acid and 5% acetonitrile (A) and acetonitrile containing 0.1% acetic acid (B) at a flow rate of 0.7 ml/min (Enderle et al, 2017). Kim et al (2017) described a simple and reliable UPLC–MS/MS method for the quantification of tadalafil from human plasma. A simple PPT with acetonitrile was used for the extraction of analyte and the IS.…”

“…The matrix effect was tested at three concentration of quality control and was found to be <12.4% for tadalafil under optimized extraction conditions. The chromatographic separation was achieved using a Shiseido C 18 column and an isocratic mobile phase consisting of 2.0 mM ammonium acetate containing 0.1% formic acid and acetonitrile containing 0.1% formic acid (55:45, v/v) at a flow rate of 0.7 ml/min (Kim et al, 2017). Nagaraju, Kodali, and Datla (2018) developed a selective LC–MS/MS method for the simultaneous estimation of tadalafil and finasteride in human plasma.…”

Simultaneous determination of citalopram and tadalafil by the second derivative synchronous fluorescence method in biological fluids; application of Box–Behnken optimization design

“…Tadalafil relaxes the neck muscle of the bladder to relieve benign prostatic hyperplasia symptoms [ 19 ] and is chemically known as [pyrazino‐[1′,2′:1,6]pyrido[3,4‐b] indole‐1,4‐dione,6(1,3‐benzodioxol‐5‐yl)2,3,6,7,12,12a‐hexahydro‐2‐methyl‐,(6R,12aR)] [ 20,21 ] (Figure 2). Various chromatographic, [ 22–28 ] spectrophotometric, [ 29–35 ] voltammetric [ 36 ] and spectrofluorimetric analytical methods have been applied for tadalafil determination. [ 37,38 ]…”