Simultaneous assay of sildenafil and desmethylsildenafil in human plasma using liquid chromatography–tandem mass spectrometry on silica column with aqueous–organic mobile phase

Eerkes, Angela; Addison, Tom; Weng, Naidong

doi:10.1016/s1570-0232(01)00602-x

Cited by 75 publications

(59 citation statements)

References 15 publications

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“…12) Since the lower limit of quantification was 1 ng/mL, a value below 1 ng/mL was taken as zero, and the data were expressed as nmol/L (nM). Pharmacokinetic variables: The pharmacokinetic variables calculated included the peak concentration (C max ), the area under the concentration versus time curve from time zero to 6 hours after the administration of sildenafil (AUC 0-6h ), and the time to reach C max (T max ).…”

Section: Methodsmentioning

confidence: 99%

Acute Effect of Sildenafil Is Maintained in Pulmonary Arterial Hypertension Patients Chronically Treated With Bosentan

et al. 2011

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SummaryThe chronic use of bosentan has been reported to reduce the plasma concentration of sildenafil. However, it remains unclear how sildenafil exerts the effect at reduced concentrations in pulmonary arterial hypertension (PAH) patients chronically treated with bosentan.We examined the hemodynamic effects of sildenafil (50 mg) in 8 Japanese patients with PAH, and simultaneously measured the plasma concentration of sildenafil ([Sil]) and its major metabolite, desmethylsildenafil ([Des]).The overall effects of sildenafil were 12.4% decrease in mean pulmonary arterial pressure, 19.9% increase in cardiac index (CI), and 25% reduction in derived pulmonary vascular resistance (PVR). When the patients were divided into two groups, a group with bosentan pretreatment [BOS (+), n = 4] and a group without bosentan pretreatment [BOS (-), n = 4], both [Sil] and [Des] were lower at the peak concentration (C max ) and the area under the plasma concentration versus time curve (AUC 0-6h ), and the time to reach C max was longer in BOS (+), although only the difference in AUC 0-6h of [Des] reached statistical significance (P = 0.02). In spite of lower concentration, the effect of sildenafil on CI was maintained in the BOS (+) group, while the decrease in PVR was less marked.Sildenafil acutely dilated the pulmonary artery and increased CI in the PAH patients. These effects were still observed or maintained in the PAH patients chronically treated with bosentan, even when [Sil] was reduced. (Int Heart J 2011; 52: 233-239)

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Section: Methodsmentioning

confidence: 99%

Acute Effect of Sildenafil Is Maintained in Pulmonary Arterial Hypertension Patients Chronically Treated With Bosentan

et al. 2011

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“…Serum sildenafil levels were measured by liquid chromatography-tandem mass spectrometry (Covance Laboratories, Indianapolis, Ind) as previously described. 19 …”

Section: Measurement Of Serum Lactate and Sildenafil Levelsmentioning

confidence: 99%

Sildenafil Improves Exercise Hemodynamics and Oxygen Uptake in Patients With Systolic Heart Failure

et al. 2007

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Background-Heart failure (HF) is frequently associated with dysregulation of nitric oxide-mediated pulmonary vascular tone. Sildenafil, a type 5 phosphodiesterase inhibitor, lowers pulmonary vascular resistance in pulmonary hypertension by augmenting intracellular levels of the nitric oxide second messenger, cyclic GMP. We tested the hypothesis that a single oral dose of sildenafil (50 mg) would improve exercise capacity and exercise hemodynamics in patients with chronic systolic HF through pulmonary vasodilation. Methods and Results-Thirteen patients with New York Heart Association class III HF underwent assessment of right heart hemodynamics, gas exchange, and first-pass radionuclide ventriculography at rest and with cycle ergometry before and 60 minutes after administration of 50 mg of oral sildenafil. Sildenafil reduced resting pulmonary arterial pressure, systemic vascular resistance, and pulmonary vascular resistance, and increased resting and exercise cardiac index (PϽ0.05 for all) without altering mean arterial pressure, heart rate, or pulmonary capillary wedge pressure. Sildenafil reduced exercise pulmonary arterial pressure, pulmonary vascular resistance, and pulmonary vascular resistance/ systemic vascular resistance ratio, which indicates a selective pulmonary vasodilator effect with exercise. Peak V O 2 increased (15Ϯ9%) and ventilatory response to CO 2 output (V E/V CO 2 slope) decreased (16Ϯ5%) after sildenafil treatment. Improvements in right heart hemodynamics and exercise capacity were confined to patients with secondary pulmonary hypertension (rest pulmonary arterial pressure Ͼ25 mm Hg). Conclusions-The present study shows that in patients with systolic HF, type 5 phosphodiesterase inhibition with sildenafil improves peak V O 2 , reduces V E/V CO 2 slope, and acts as a selective pulmonary vasodilator during rest and exercise in patients with HF and pulmonary hypertension.

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“…In our laboratory, we have successfully used Quadra™ 96 for simultaneous protein precipitation , solid-phase (Shou et al, , 2002cChen et al, 2002;Eerkes et al, 2002a;Naidong et al, 2002a) and liquid-liquid (Eerkes and Naidong, 2003) extraction of 96 samples. Inadequate sensitivity was obtained when protein precipitation extraction was attempted for which the plasma size is typically limited to <0.10 mL.…”

Section: Extractionmentioning

confidence: 99%

Development and validation of a hydrophilic interaction liquid chromatography–tandem mass spectrometric method for the analysis of paroxetine in human plasma

Weng

Eerkes

2003

Biomedical Chromatography

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A sensitive, simple, fast and rugged hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS) method for the determination of paroxetine was developed and validated over curve range 0.050-50 ng/mL using only 0.4 mL plasma. This is the first published LC-MS/MS method and the low limit of quantitation of this method is 10-fold lower than previously published methods. A simple liquid-liquid extraction method using methyl-tert butyl ether (MTBE) as the extraction solvent was used to extract paroxetine and the internal standard (IS) fentanyl-d(5) from plasma. The extract was evaporated to dryness, reconstituted and injected onto a silica column using a low aqueous-high organic mobile phase. The chromatographic run time was 2.0 min per injection, with retention times of 1.1 and 1.2 min for paroxetine and IS, respectively. The detection was by monitoring paroxetine at m/z 330 --> 192 and IS at m/z 342 --> 188, respectively. The inter-day precision and accuracy of the quality control (QC) samples were <5.0% relative standard deviation (RSD) and <2.9% relative error (RE). This method can be used for supporting therapeutical drug monitoring and pharmacokinetic or drug-drug interaction studies.

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Simultaneous assay of sildenafil and desmethylsildenafil in human plasma using liquid chromatography–tandem mass spectrometry on silica column with aqueous–organic mobile phase

Cited by 75 publications

References 15 publications

Acute Effect of Sildenafil Is Maintained in Pulmonary Arterial Hypertension Patients Chronically Treated With Bosentan

Acute Effect of Sildenafil Is Maintained in Pulmonary Arterial Hypertension Patients Chronically Treated With Bosentan

Sildenafil Improves Exercise Hemodynamics and Oxygen Uptake in Patients With Systolic Heart Failure

Development and validation of a hydrophilic interaction liquid chromatography–tandem mass spectrometric method for the analysis of paroxetine in human plasma

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