Polarographic behaviour and determination of spironolactone

Abstract

Abstract. The polarographic behaviour of spironolactone in Britton-Robinson buffers containing 40~ methanol as a solubilizer was studied. Over the pH range 3-12 a cathodic wave was produced. The wave was characterized as irreversible, diffusion-controlled and partially affected by adsorption phenomena. The number of electrons involved in the reduction was found by coulometric measurements at a controlled potential. A method was developed for the determination of spironolactone in tablets and the results obtained were in agreement with those obtained by the B.P. 1988 method. The mechanism of the electrode reaction is discussed.Key words: spironolactone, polarography, dosagi forms, pharmaceutical analysis Spironolactone is a steroid that acts as a competitive antagonist of the endogenous mineralocorticoid aldosterone. It is indicated in the treatment of essential hypertention, oedema associated with congestive heart failure, hepatic cirrhosis with ascites, the nephroti¢ syndrome and idiopathic oedema. By blocking the sodiumretaining effects of aldosterone, spironolactone corrects one of the most important mechanisms responsible for the production of oedema. It is rapidly metabolised after oral administration. The metabolites are excreted largely in the urine, but also in the bile [1].As a result of the widespread therapeutic use of spironolactone, much attention has been paid to its determination either alone or in combination with other drugs or metabolites. The USP XXII [2] recommends HPLC for the determination of spironolactone whether alone or in combination with hydrochlorothiazide. On the other hand, the B.P. 1988 [3] describes a direct spectrophotometric method. Other methods reported include spectrophotometry [-4-8], fluorimetry [9][10][11], TLC [12,13], HPLC [14][15][16][17] and GC-MS [18,19], but no polarographic studies seem to have been made hitherto.

Analysis of spironolactone residues in industrial wastewater and in drug formulations by cathodic stripping voltammetry

“…The value of the electron transfer coefficient ( α ) involved in the rate determining step was calculated employing the following equation [21] : where n α is the number of electron transfer in the rate determining step. Assuming n α is equal 1 or 2, the computed values of α from the linear plots of linear plots of log ν vs. E p , c 1 of peak I and log ν vs. E p , c 2 of peak II were found higher than 0.6 confirming the irreversible nature of the observed reduction steps [13] , [20] . This trend is also indicative of kinetic complications in the electrode process and the reduction process comprises several reactions including adsorption [13] , [19] .…”

“…In the CV, a small reduction peak current at high ν corresponding to peak I was noticed. Thus, it can be concluded that, the reduction step undergoes a very rapid follow-up chemical reaction [13] , [14] . The dependence of the CV response on analyte concentration at pH 9.0 showed no significant changes on the cathodic current of the observed cathodic peak at −1.20 V, indicating that the electrochemical process is a typical of ECE type electrochemical mechanism [19] .…”

“…Representative DPCSVs are shown in Fig.1 . The DPCSVs of the SP drug solutions at pH lower than 7.0 displayed one reduction peak at −1.05 V ( E p , c 1 )H assigned to the reduction of the carbonyl group of pregn-4-ene-21-carboxylic acid, 7-(acetylthio)-17-hydroxy-3-oxo, γ-lactone (7α, 17α)-, aldactone to pregn-4-ene-21-carboxylic acid, 7-(acetylthio)-17-hydroxy-3-hydroxy-, γ-lactone (7α, 17α)-, aldactone in two electrons reduction step (2H + /2e) [13] ( Scheme 1 ). In solutions of 7<pH<10, the DPCSVs of SP drug showed two peaks in the range from −1.11 to −1.20 V (peak I, E p , c 1 ) and from −1.36 to −1.46 V (peak II, E p,c2 ) and were safely assigned to successive reduction of the SP drug in two consecutive reduction steps (H + /e) [18] , [19] .…”

“…Polarographic [13] and square-wave adsorptive cathodic stripping voltammetric (SW-AdSV) [14] have been developed for SP determination in drug formulations at dropping mercury electrode (DME) and hanging mercury drop electrode (HMDE) at pH 2–3, respectively. The selectivity and detection limit of polarographic method [13] are not compatible with the low level of SP residues in wastewater. On the other hand, in SW-ACSV method [14] , peak resolution and selectivity of the observed cathodic peak at −1.15 V were also not compatible for analysis of SP residues in wastewater.…”

Recent Advances in the Analysis of Steroid Hormones and Related Drugs

“…In the majority of cases differential pulse polarography, based on the reduction of the 4-ene-3-oxo group is used, for e.g. spironolactone, 231 beclomethasone dipropionate, 232 dexamethasone sodium phosphate 233 and betamethasone valerate. 234 Gestodene was determined in oral contraceptives by square-wave voltammetry and adsorptive stripping techniques.…”