Abstract
Quick and accurate methods for determination of carvedilol and hydrochlorothiazide in tablets and spiked human plasma by using third derivative (3D), fourth derivative (4D) and ratio spectra derivative (1DD) spectrophotometric methods were developed. The zero-crossing technique was employed in measurements, using 3D at 245.9 or 230.2 nm and 4D at 247.4 or 226.9 nm for carvedilol or hydrochlorothiazide, respectively. The first-derivative of ratio spectra (1DD) where the amplitudes were measured at 236.1 nm for carvedilol and 261.1 nm for hydrochlorothiazide. The calibration curves were linear in the ranges of 1.0-20.0 μg mL-1 for each of carvedilol and hydrochlorothiazide using 3D 4D and 1DD methods. The suggested methods were tested using laboratory-prepared mixtures and were successfully applied for the analysis of pharmaceutical formulations. The methods retained their accuracy and precision when the standard addition technique was applied. The results obtained by applying the proposed methods were statistically analyzed and compared with those obtained by reported and official HPLC methods for carvedilol and hydrochlorothiazide, respectively. These methods showed to be appropriate for simultaneous determination of carvedilol and hydrochlorothiazide in human plasma samples with a limit of quantitation (LOQ) is ≤ 0.5 μg mL-1.
Highlights
Carvedilol (CARV, Figure 1), 1-(9H-carbazol-4-yloxy)-3-[[2-(2methoxyphenoxy) ethyl]amino]-2-propanol, which is a nonselective ß-adrenergic blocker with α 1-blocking activity [1]
The purpose of the present study is to investigate the utility of third or fourth derivative and first derivative of ratio spectrophotometric methods in the assay of carvedilol and hydrochlorothiazide in combination in the pharmaceutical formulations without the necessity of sample treatment
Zero–order absorption spectra of CARV and HCT (Figure 2) show strong spectral overlap, which interfere with direct spectrophtometric analysis of the studied drugs
Summary
Carvedilol (CARV, Figure 1), 1-(9H-carbazol-4-yloxy)-3-[[2-(2methoxyphenoxy) ethyl]amino]-2-propanol, which is a nonselective ß-adrenergic blocker with α 1-blocking activity [1]. It is used in the treatment of sever heart failure, bradycardia and hypertension [2]. It is administered alone or together with antihypertensive, combined therapy of CARV and HCT had a significantly greater blood pressure reduction than with the same dosage of the drug alone [3]. Hydrochlorothiazide (HCT, Figure 1), 6-chloro-3,4-dihydro2H-1,2,4-benzothiadiazine-7-sulfonamide-1,1–dioxide, is a diuretic of the class of benzothiadiazines widely used in antihypertensive pharmaceutical formulations which decreases active sodium reabsorption and reduces peripheral vascular resistence [4]
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