Quantification of Propranolol in Rat Plasma by LCMS/MS Using Tramadol as an Internal Standard for Pharmacokinetic Studies in TAA-induced Liver Fibrotic Rats | Chapter 9 | Trends in Pharmaceutical Research and Development Vol. 1

A simple, rapid and selective liquid chromatography coupled with tandem mass spectrometry (LCMS/MS) is developed and validated for quantification of propranolol without the sample extraction step in rat plasma using tramadol as an internal standard (IS). The analytes are separated using an isocratic mobile phase which consist of methanol and 10 mm ammonium formate (70/30, v/v) on an isocratic UK-C18 (Imtakt Unison 2.0 × 50 mm, 3 μm) column and was analyzed by MS/MS in the multiple reaction monitoring (MRM) mode using the transitions of respective (M+H)+ ions, m/z 260.0→116.2 and m/z 264.2→58.2 for quantification of propranolol and IS, respectively. The standard calibration curves showed good linearity within the range of 2.0 to 800.0 ng/ml (r2 = 0.999, 1/x2 weight). The lower limit of quantification (LLOQ) was 2 ng/ml. The retention time of propranolol and IS were 1.12 and 0.939 min which means that it is the potential for the high-through put potential of the proposed method. In addition, no significant metabolic compounds were found to interfere with the analysis. Acceptable precision and accuracy were obtained for the concentrations over the standard curve range. The validated method was successfully applied for the pharmacokinetic studies after 2 mg/kg of propranolol HCl in the thioacetamide (TAA)-induced fibrotic rats

Author(s) Details

Ju-Seop Kang
Department of Pharmacology, Clinical Pharmacology Lab, College of Medicine, Hanyang University, Seoul 133-791, South Korea.

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Pharmacological Profile and Indications of Non-Vitamin K Antagonist Oral Anticoagulants: Updated Review | Chapter 06 | Modern Advances in Pharmaceutical Research Vol. 2

The non-vitamin K antagonist oral anticoagulants have been approved since 2008 for the prevention of systemic embolism and stroke in patients with non-valvular atrial fibrillation with prior stroke, transient ischemic attack, or CHA2DS2-VASc score ≥2. According to the latest guidelines, if CHA2DS2-VASc score ≥2 for all male patients or if CHA2DS2-VASc score ≥3 for all female patients, oral anticoagulants are recommended, and considering shared decision between doctor and patient. However, they are contraindicated in patients with mechanical prosthetic valve and in patients with moderate-to-severe mitral stenosis and atrial fibrillation. They have also been approved for prevention and treatment of deep vein thrombosis and pulmonary embolism. Dabigatran, a direct thrombin inhibitor, was the first to be approved, followed by the factor Xa inhibitors, rivaroxaban, apixaban, and in 2015, edoxaban. They have advantages such as the use of fixed-dose, with infrequent drug interaction, rapid onset of action and do not require monitoring of their anticoagulant action. Nonetheless, they have different half-lives, the need for dose adjustment according to renal function, weight and age of the patient. Its use in pregnant women and children or adolescents is not well established. There are also peculiarities about the risks of bleeding, effects on coagulation tests and specific antidotes. Through this review we discuss the pharmacokinetics and pharmacodynamics characteristics of direct oral anticoagulants, its indications, interactions and contraindications. Analysis of its efficacy, safety, risk-benefit ratio and costs will also be addressed.

Author(s) Details

Rose Mary Ferreira Lisboa da Silva
Department of Internal Medicine, Faculty of Medicine, Federal University of Minas Gerais, Brazil.

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