A highly sensitive method for the quantification of fludrocortisone in human plasma using ultra‐high‐performance liquid chromatography tandem mass spectrometry and its pharmacokinetic application

Abstract

A simple and high sensitive ultra-high-performance liquid chromatography tandem mass spectrometry method for the determination of fludrocortisone in human plasma was developed and validated as per guidelines. The analyte and internal standard (IS), fludrocortisone-d5 , were extracted from human plasma via liquid-liquid extraction using tert-butyl methyl ether. The chromatographic separation was achieved on a Chromolith RP18e column using a mixture of acetonitrile and 2 mm ammonium formate (70:30, v/v) as the mobile phase at a flow rate of 0.7 mL/min. Quantitation was performed on a triple quadrupole mass spectrometer employing electrospray ionization technique, operating in multiple reaction monitoring and positive ion mode. The precursors to product ion transitions monitored for fludrocortisone and IS were m/z 381.2 → 343.2 and 386.2 → 348.4, respectively. The assay was validated with linear range of 40-3000 pg/mL. The intra- and inter-day precisions (relative standard deviation) were within 0.49-7.13 and 0.83-5.87%, respectively. The proposed method was successfully applied to pharmacokinetic studies in humans.

Assessing treatment adherence is crucial to determine adequacy of mineralocorticoid therapy

“…Endorsing the accuracy of the adherence data, sFC showed an inverse correlation with the time from the last FC dose ( r = −0.355, P = 0.023) ( Fig. 1B ), with a peak in serum concentration 1-h after administration and an estimated half-life of 1 to 3 h which is consistent with published data ( 32 , 33 , 34 ).

Figure 1 Univariate analysis for serum and urine FC levels in a cohort of 41 patients with primary adrenal insufficiency.

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Effect of Fludrocortisone on Intradialytic Hypotension: An Open-Label, Randomized, Crossover Study

“…However, our study revealed that the effect of fludrocortisone on the first half of the hemodialysis session was still promising. The mean lowest MAP, mean lowest SBP, and mean SBP in the first 2 h after hemodialysis initiation were significantly higher in patients receiving fludrocortisone which was consistent with the peak plasma fludrocortisone levels of between 0.5 and 2 h [26]. We hypothesized that fludrocortisone might reach its pharmacologic peak effect at that time, and a higher dosage might be required to maintain its effect throughout the 4-h hemodialysis.…”

Pharmacokinetics of oral fludrocortisone in septic shock

“…No data has previously been published on the pharmacokinetics of fludrocortisone in septic shock patients. The only available data were assessed in healthy volunteers but using higher single doses (between 100 μg and 2 mg) and found a wide range of plasma half‐lives between 0.5 h and 3.6 h . Our results are in this range of values (1.35 h), suggesting that fludrocortisone elimination is similar in septic shock patients and in healthy volunteers.…”