Determination of Spironolactone and Canrenone in Human Plasma by High-performance Liquid Chromatography with Mass Spectrometry Detection

Abstract

Abstract.A new simple, sensitive and LC-MS/MS method for quantification of spironolactone and its metabolite, canrenone, in human plasma is proposed. The analytes were analysed on a C18 column at 48 ºC, by using a mobile phase of 58 % methanol, 42 % 10 mmol dm −3 ammonim acetate in water and a flow rate of 1 mL/min. The detection of both analytes in plasma was performed as follows: ESI+, EIC (m/z 169;187;283;305) from m/z 341, after protein precipitation with methanol. Calibration curves were generated over the ranges 2.77-184.50 ng/mL for spironolactone and 2.69-179.20 ng/mL for canrenone by using a weighted (1/y) linear regression. The absolute values of within-and between-run precision and accuracy for both analytes ranged between 3.1 and 13.9 %, and the mean recovery was 99.7 %. The analytes demonstrated good stability in various conditions. The validated method has been applied to a bioequivalence study of 50 mg spironolactone tablets on healthy volunteers. (doi: 10.5562/cca1761)

Development and validation of a fast and sensitive UHPLC‐ESI‐MS method for the simultaneous quantification of spironolactone and its metabolites in ocular tissues

“…This is due to the cleavage of the 7 α ‐thioacetyl group of SPL during the electrospray evaporation and ionization process within the ESI source producing CAN. This was reported by Sora, Udrescu, Albu, David, and Medvedovici () and Vlase, Imre, Muntean, Achim, and Muntean (). However, the SPL signal can be easily distinguished from the CAN signal since their retention times are 2.4 and 3.0 min, respectively.…”

“…As far as we are aware, there is no available validated UHPLC–MS method in the literature allowing the simultaneous detection and quantification of spironolactone and its main metabolites, TMSPL and CAN, in corneal tissues, within a relatively short runtime of 5 min. Indeed, recent LC–MS/MS methods have been published for the quantification of spironolactone and its metabolite, CAN, in human plasma but these methods did not include TMSPL (Dong, Xu, Zhang, Tian, & Chen, ; Lee, An, Kim, Shim, & Lee, ; Sora, Udrescu, Albu, David, & Medvedovici, ; van der Nagel, Versmissen, Bahmany, Gelder, & Koch, ; Vlase, Imre, Muntean, Achim, & Muntean, ) and the runtimes were relatively long (> 10 min; Dong, Xu, Zhang, Tian, & Chen, ; Sora, Udrescu, Albu, David, & Medvedovici, ; Takkis et al, ). Including TMSPL in the analytical method is of great importance, especially now that it is recognized as being one of the main active metabolites of spironolactone (Kaukonen, Vuorela, Vuorela, & Mannermaa, ; Sandall, Millership, Collier, & McElnay, ; Sora, Udrescu, Albu, David, & Medvedovici, ) and contributes significantly to the pharmacological effects observed (Kaukonen, Vuorela, Vuorela, & Mannermaa, ; Los, Pitzenberger, Ramjit, Coddington, & Colby, ; H. W. Overdiek, Hermens, & Merkus, ; Sandall, Millership, Collier, & McElnay, ).…”

Determination and Occurrence of Mineralocorticoids in Taihu Lake of China

“…In contrast to its metabolites, spironolactone was not detected at all in that study. The phenomenon could be explained that spironolactone could be rapidly metabolized in humans to canrenone and 7α-thiomethyl spironolactone (Vlase et al, 2011) and fast degrade in contact with activated sludge and in aqueous solutions (Sulaiman et al, 2015). This pattern is different from that found in the river waters downstream from pharmaceutical manufacture discharges where spironolactone (402-14,681 ng/L) was measured with detected with higher levels of canrenone (226-7,336 ng/L) (Creusot et al, 2014).…”

“…Creusot et al (2014) revealed the concentrations of spironolactone and canrenone up to 2.9 μg/L downstream of a French pharmaceutical factory. It was reported that spironolactone could be rapidly metabolized into canrenone, 7α-thiomethyl spironolactone and other metabolites in the body (Sadee et al, 1973;Vlase et al, 2011) and could fast degrade in contact with activated sludge and in aqueous solutions (Sulaiman et al, 2015).…”

Optimization and Validation of a Sensitive HPLC–PDA Method for Simultaneous Determination of Torasemide and Spironolactone in Human Plasma using Central Composite Design

“…These methods include quantification by spectrophotometry, 4,5 HPLC, [6][7][8][9][10][11][12] and capillary electrophoresis. 13 Although, there are no published analytical methods available for determination of SPI alone; but a thorough literature review revealed quite a few methods available for the determination of SPI in combination with its metabolites, [14][15][16][17][18][19] degradation products 20 and other drugs. [21][22][23][24][25][26][27] However, an intensive literature search revealed to the best of our knowledge that only eight methods are available for simultaneous determination of TOR and SPI.…”