Validated UPLC-MS/MS assay for the determination of synthetic phosphodiesterase type-5 inhibitors in postmortem blood samples

Proença, Paula; Mustra, Carla; Marcos, Mariana; Franco, João Miguel; Côrte-Real, F.; Vieira, Duarte Nuno

doi:10.1016/j.jflm.2013.03.002

Cited by 15 publications

(13 citation statements)

References 30 publications

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“…Tadalafil is a chiral substance with 2 stereogenic centers, and its molecular structure significantly differs from those of achiral sildenafil and vardenafil. 1,[3][4][5] In the case of tadalafil (Figure 1), many studies have been devoted to the differentiation of counterfeit from genuine Cialis® tablets. 1 Various clinically important side effects have been described for PDE-5 inhibitor drugs, such as headache, back pain, or visual disorder.…”

Section: Introductionmentioning

confidence: 99%

“…1 Various clinically important side effects have been described for PDE-5 inhibitor drugs, such as headache, back pain, or visual disorder. 5,[8][9][10] Counterfeit medicines containing tadalafil were also studied by nuclear magnetic resonance (NMR), 11 Raman, 11 and infrared (IR) spectroscopies 7,12,13 or X-ray fluorescence. The restrictions and patient's desire for anonymity naturally led to illegal distribution of various imitations and counterfeits containing PDE-5 inhibitors or their analogues.…”

Section: Introductionmentioning

confidence: 99%

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Chiroptical and vibrational spectroscopic study of genuine and counterfeit medicines containing tadalafil

et al. 2018

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The production and distribution of counterfeit pharmaceuticals present a serious problem worldwide. This is true especially in case of phosphodiesterase type 5 inhibitors for treating erectile dysfunction, where consumers often prefer buying them anonymously from unverified sources. In this study, genuine and counterfeit Cialis® 20 mg tablets were analyzed by electronic circular dichroism, vibrational circular dichroism, and infrared spectroscopy. The characteristic spectral patterns were identified by comparison with the spectra of tadalafil standard as an active pharmaceutical ingredient, and its presence was confirmed in all samples. The amount of tadalafil, however, was markedly lower in the case of counterfeit tablet as the observed band intensities were considerably lower. No other significant differences between the genuine and counterfeit tablets were revealed. Ab initio density functional theory calculations provided a detailed description of the stable conformers of tadalafil in a solution and enabled thorough interpretation of the experimental spectra.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Chiroptical and vibrational spectroscopic study of genuine and counterfeit medicines containing tadalafil

et al. 2018

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“…[11] In recent pharmacokinetic studies, LC-tandem mass spectrometry (LC-MS/MS) has primarily been used for measuring tadalafil in plasma because of its high sensitivity and selectivity. [12][13][14][15][16][17][18][19] Proença et al published a validated ultra-performance liquid chromatography (UPLC)-MS/ MS method for the analysis of sildenafil, vardenafil, and tadalafil in postmortem blood samples. [17] Lee et al also reported an LC-MS/MS method for the determination of five ED drugs and their selected metabolites in hair to monitor abuse of mirodenafil, sildenafil, tadalafil, udenafil and vardenafil.…”

Section: Introductionmentioning

confidence: 99%

“…[12][13][14][15][16][17][18][19] Proença et al published a validated ultra-performance liquid chromatography (UPLC)-MS/ MS method for the analysis of sildenafil, vardenafil, and tadalafil in postmortem blood samples. [17] Lee et al also reported an LC-MS/MS method for the determination of five ED drugs and their selected metabolites in hair to monitor abuse of mirodenafil, sildenafil, tadalafil, udenafil and vardenafil. [18] However, these methods required a relatively long run time, over 5 min, [14][15][16][17][18] which is not suitable for high-throughput tadalafil determination.…”

Section: Introductionmentioning

confidence: 99%

“…[17] Lee et al also reported an LC-MS/MS method for the determination of five ED drugs and their selected metabolites in hair to monitor abuse of mirodenafil, sildenafil, tadalafil, udenafil and vardenafil. [18] However, these methods required a relatively long run time, over 5 min, [14][15][16][17][18] which is not suitable for high-throughput tadalafil determination. Thejomoorthy et al reported a sensitive LC-MS/ MS method for tadalafil determination in rat plasma with the linearity range 0.5 to 1,000 ng/ml using liquid-liquid extraction (LLE) method, but it required large amounts of extraction sol-…”

Section: Introductionmentioning

confidence: 99%

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

Kim

Nam

Kwon

et al. 2017

Transl Clin Pharmacol

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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).

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Pharmacokinetic and Bioequivalence Evaluation of 2 Tadalafil Tablets in Healthy Male Chinese Subjects Under Fasting and Fed Conditions

Shao

Yang

Ruan

et al. 2021

Clinical Pharm in Drug Dev

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Tadalafil is an effective, reversible, and competitive phosphodiesterase 5 inhibitor mainly used to treat erectile dysfunction. This study investigated the bioequivalence of generic and marketed formulations of 10‐mg tadalafil tablets under fasted and fed conditions. This open‐label, randomized, single‐dose, 2‐period crossover study included 53 healthy Chinese men (aged 20‐43 years). Plasma samples were collected from 0.5 hours before treatment to 72 hours after each dose and analyzed using ultra‐high‐performance liquid chromatography coupled with tandem mass spectrometry. Pharmacokinetic parameters were calculated using noncompartmental analysis. Safety assessments were performed throughout the study. For the fasted state, the 90% confidence intervals of the geometric mean ratios between the generic and marketed formulations were 86.1% to 99.1% for the maximum plasma concentration and 88.4% to 100.3% for the area under the plasma concentration–time curve from time 0 to infinity, and the corresponding values under the fed state were and 99.9% to 108.4% and 95.7% to 104.3%, respectively. All data were within the accepted bioequivalence range of 80% to 125%. After consuming high‐fat, high‐calorie meals in the fed condition, the time to the maximum plasma concentration was similar between the formulations, and area under the plasma concentration–time curve from time 0 to infinity and maximum plasma concentration were 10.2% and 6.55% higher, respectively, for the marketed formulation. Thus, food had no clinically relevant effect on tadalafil exposure following a single oral dose in healthy Chinese men. No serious adverse reactions were reported. These results indicated that the analyzed generic and marketed tadalafil tablets were bioequivalent with similar safety profiles.

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Validated UPLC-MS/MS assay for the determination of synthetic phosphodiesterase type-5 inhibitors in postmortem blood samples

Cited by 15 publications

References 30 publications

Chiroptical and vibrational spectroscopic study of genuine and counterfeit medicines containing tadalafil

Chiroptical and vibrational spectroscopic study of genuine and counterfeit medicines containing tadalafil

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

Pharmacokinetic and Bioequivalence Evaluation of 2 Tadalafil Tablets in Healthy Male Chinese Subjects Under Fasting and Fed Conditions

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