Spironolactone: Diversity in Metabolic Pathways

Karim, Aziz; Hribar, Jeremy D.; Doherty, Margaret M.; Aksamit, William; Chappelow, D.; Brown, Edward A.; Markos, Charles S.; Chinn, Leland J.; Liang, Donghai; Zagarella, J.

doi:10.3109/00498257709038680

Cited by 24 publications

(3 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1 -3 After oral administration, spironolactone is extensively metabolized to a large number of compounds that can be divided into two classes. 4,5 In the first group, the sulfur atom of the parent drug is retained in the molecule. The second group is formed by the dethioacetylation of spironolactone and subsequent biotransformation steps.…”

Section: Introductionmentioning

confidence: 99%

Simultaneous determination of spironolactone and its active metabolite canrenone in human plasma by HPLC‐APCI‐MS

Dong

Zhang

et al. 2006

J. Mass Spectrom.

View full text Add to dashboard Cite

A sensitive and specific liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry (LC-APCI-MS) method for the simultaneous determination of spironolactone and its active metabolite canrenone in human plasma has been developed and validated. After the addition of estazolam as the internal standard (IS), plasma samples were extracted with methylene chloride : ethyl acetate mixture (20 : 80, v/v) and separated by high-performance liquid chromatography (HPLC) on a reversed-phase C18 column with a mobile phase of methanol-water (57 : 43, v/v). Analytes were determined in a single quadrupole mass spectrometer using an atmospheric pressure chemical ionization (APCI) source. LC-APCI-MS was performed in the selected-ion monitoring (SIM) mode using target ions at m/z 341.25 for spironolactone and canrenone, m/z 295.05 for estazolam. The method was proved to be sensitive and specific by testing six different plasma batches. Calibration curves of spironolactone and canrenone were linear over the range 2-300 ng/ml. The within- and between-batch precisions (relative standard deviation (RSD)%) were lower than 10% and the accuracy ranged from 85 to 115%. The lower limit of quantification (LLOQ) was identifiable and reproducible at 2 ng/ml. The proposed method was successfully applied to study the pharmacokinetics of spironolactone and its major metabolite in healthy male Chinese volunteers.

show abstract

Section: Introductionmentioning

confidence: 99%

Simultaneous determination of spironolactone and its active metabolite canrenone in human plasma by HPLC‐APCI‐MS

Dong

Zhang

et al. 2006

J. Mass Spectrom.

View full text Add to dashboard Cite

show abstract

“…Plasma protein binding is extensive (88-98%) and occurs to both human serum albumin and ␣ 1 -acid glycoprotein [16,17]. Spironolactone is rapidly and extensively metabolized to a large number of metabolites [15,16,18,19]. The major metabolic pathways of spironolactone result in the formation of 7␣-thiomethylspirolactone (2, Fig.…”

Section: Introductionmentioning

confidence: 99%

Development and validation of an HPLC method for the determination of spironolactone and its metabolites in paediatric plasma samples

Sandall

Millership

Collier

et al. 2006

Journal of Chromatography B

View full text Add to dashboard Cite

“…Furaneol itself was first reported as a significant compound in pineapple [l] but has since also been claimed as a character impact-compound in strawberries [2,3] and beef [4] as well as being present in arctic bramble [q, popcorn [6], roasted filberts [A, and wine [8]. Furaneol methyl ether (2,5-dimethyl-4-methoxy-3-(2H)-furanone) too has been reported in mango [9], artic bramble [q, strawberry [lo], and wine [8], and similarcompounds 2,5-dimethyl-3-(2H)-furanone [9,11,12,13,14], 4-hydroxy-5methyl-3-(2H)-furanone [15,1 T] and 2,4,5-trimethyl-3-(2H)-furanone 1181 have been found in such diverse products as beef, bread, coffee, mangoes, leeks, and onions.…”

mentioning

confidence: 99%