Objective: Direct and sensitive spectrophotometric method is described for the quantitative determination of some anti-hypertensive drugs such as atenolol (ATN) and timolol (TIM) in pure forms as well as in their dosage forms. Methods:The proposed method is based on the redox reaction between the selected drugs and KMnO4 in alkaline medium. The method involves treating the aqueous solution of the selected drugs with KMnO4 in alkaline medium and measuring the bluish-green product at 610 nm. The different experimental parameters affecting the development and stability of the color were carefully studied and optimized. Results:The fixed-time method is adopted for constructing the calibration curves, which were found to be linear over the concentration ranges of 2.0-14 µg/ml and 2.0-28 µg/ml for ATN and TIM, respectively. The determination of the studied drugs by initial rate, variable time and rate constant method was workable with the calibration equations obtained but the fixed time method has been found to be more applicable. Conclusion:The applicability of the proposed method was demonstrated by the determination of the selected drugs in both pure and in commercial dosage forms and has met the validation requirements.
The burden of depression and other mental disorders is on the rise globally, and successful treatment sometimes requires modifications of drugs and/or dose regimens. The development of novel analytical methods for the determination of antidepressant drugs in biological fluids is thus urgently required. Herein, a sensitive, robust, and rapid liquid chromatographic coupled tandem mass spectrometric method was developed and validated for the determination of citalopram (CIT) and sertraline (SER) in rat plasma after oral administration. The analytes of interest and internal standard (duloxetine (DUL)) were extracted from 100 μL of plasma with solid-phase extraction on an Oasis HLB cartridge followed by the separation with gradient elution with water containing 0.1% formic acid and acetonitrile on an Agilent Eclipse Plus ODS (4.6 × 100 mm, 3.5 μm) column at flow rate 0.2 mL min −1 . The triple quadrupole mass spectrometry was applied via electrospray ionization source for detection. The fragmentation pattern of the protonated CIT, SER, and DUL was elucidated using multiple reaction monitoring of the transitions of m/z 325.2 to 109, 306.1 to 158.9, and 298.1 to 154.1 as [M + H] + for CIT, SER, and DUL, respectively. The proposed method has been validated as per US-FDA bioanalytical guidelines in terms of linearity, accuracy, precision, matrix effects, stability, selectivity, and recovery. The method was linear over the concentration range of 1−2000 and 1−1000 ng mL −1 with the lower limit of detection of 0.12 and 0.19 ng mL −1 for CIT and SER, respectively. The interday and intraday precisions and accuracy expressed by the relative standard deviation and the relative standard error were both lower than 11.1% and 2.1%, respectively. The proposed method was successfully applied for the pharmacokinetics and drug monitoring studies of CIT and SER in rat plasma after a single oral dose of 120 mg kg −1 of CIT and SER. Coadministration of SER with CIT has affected the peak plasma concentrations, maximum plasma concentration time, area under the concentration−time curve, and oral clearance of CIT. Molecular modeling study showed that SER could competitively inhibit CYP2D6, the main enzyme involved in CIT metabolism. A possible drug−drug interaction in psychiatric patients undergoing chronic SER and CIT treatment is therefore worthy of more attention in an effort to avoid side effects and serotonin syndrome.
Two simple, rapid and selective spectrophotometric methods have been developed for the analysis of the psychoactive drug thioridazine HCl (TRH) in tablets and in biological fluids. The first method is based on the oxidation of TRH by a known excess of N-bromosuccinimide (NBS), followed by the determination of unreacted oxidants by measuring the decrease in absorbance of two different dyes; amaranth (AM) and methylene blue (MB) at a suitable l max 520 and 660 nm, respectively. Beer-Lambert plots showed good correlation in the concentration ranges of 0.8-4.8 and 0.8-5.6 µg/ml for AM and MB methods, respectively. The second method is based upon the formation of an ion-pair complexes (1: 1) with the acidic sulphonphthalein dyes bromophenol blue (BPB) and bromothymol blue (BTB). The formed complexes were extracted into methylene chloride and their absorbance was measured at 405 and 408 nm for BPB and BTB, respectively. Beer's law was obeyed with a good correlation coefficient (r = 0.9995-0.9989) in the concentration ranges of 4 -24 µg/ml for both BPB and BTB methods, respectively. All measurements of the two procedures are carried out in an acidic medium at room temperature. Optimizations of the different experimental conditions are described for both methods. The two methods have been successfully applied to the determination of thioridazine HCl in pharmaceutical, serum and urine samples and average recoveries are in the range of 98.12 -102.55%. Analytical results obtained with this novel method are satisfactory.
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