title: A highly sensitive LC-MS/MS method for concurrent determination of sildenafil and rosiglitazone in rat plasma.
abstract: Patients with pulmonary arterial hypertension (PAH) are currently treated with more than one drug. Sildenafil, a phosphodiesterase type 5 (PDE-5) inhibitor, and rosiglitazone, a peroxisome proliferator-activated receptor γ (PPAR-γ) activator, is one of those combinations that could be used in PAH. To monitor the pharmacokinetics of sildenafil in the presence of rosiglitazone, we have developed and validated a sensitive, specific and rapid liquid chromatography-tandem mass spectrometric (LC-MS/MS) method. We have used this validated method to study the pharmacokinetics of sildenafil and rosiglitazone after intravenous administration of sildenafil alone or a combination of sildenafil plus rosiglitazone to adult male Sprague-Dawley rats. Sildenafil and rosiglitazone were extracted from plasma by protein precipitation with methanol. With an octadeuterated sildenafil as the internal standard, the drugs were separated via gradient elution using a C18 column and formic acid in methanol or in water as the mobile phase with a flow rate of 0.25mL/min. Both sildenafil and rosiglitazone samples in rat plasma produced linear response, when the concentration ranged between 5 and 1000ng/mL (r(2)>0.99). The pharmacokinetics study suggests that intravenous co-administration rosiglitazone plus sildenafil increases the plasma concentration of sildenafil and extends the drug's elimination half-life.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, 1300 Coulter St., Amarillo, TX 79106, United States.
authors.forename: Jahidur
authors.initials: J
authors.lastname: Rashid
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, 1300 Coulter St., Amarillo, TX 79106, United States. Electronic address: fakhrul.ahsan@ttuhsc.edu.
authors.forename: Fakhrul
authors.initials: F
authors.lastname: Ahsan
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods / Q000592:standards*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D000077154:Rosiglitazone; D000068677:Sildenafil Citrate / Q000008:administration & dosage / Q000032:analysis / Q000097:blood*; D053719:Tandem Mass Spectrometry / Q000379:methods / Q000592:standards*; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000032:analysis / Q000097:blood*
chemical_list: D045162:Thiazolidinediones; D000077154:Rosiglitazone; D000068677:Sildenafil Citrate
keywords: Inhalational therapy; LC–MS/MS; Pharmacokinetics; Pulmonary arterial hypertension; Rosiglitazone; Sildenafil