Probenecid with bumetanide

Brater DC, Fox WR, Chennavasin P. Interaction studies with bumetanide and furosemide. Effects of probenecid and of indomethacin on response to bumetanide in man. J Clin Pharmacol (1981)21,647-53. 

Chromatograms of (a) urine matrix, (b) urine matrix spiked with a mixture of 1 pg/mL of each diuretic and (c) an aqueous solution of the diuretics, all eluted with a 0.042 M SDS-4% 1-propanol mobile phase in phosphate buffer at pH 4.5. Compounds (1) furosemide, (2) chlorthalidone, (3) ethacrynic acid, (4) bendroflumethiazide, (5) probenecid, (6) bumetanide, (7) amiloride, (8) xipamide, (9) spironolactone and (10) triamterene. Reprinted from Ref 23 with permission of Elsevier. 

Probenecid has been reported to inhibit renal elimination of many drugs acyclovir (325,326), allopurinol (327), bumetanide (328), cephalosporins (329-334), cidofovir (335), ciprofloxacin (336), famotidine (337), fexofenadine (338), furosemide (339), and oseltamivir (Ro 64-0802) (340). Recent studies have elucidated that probenecid is a potent inhibitor of renal organic anion transporters (OAT1 and OAT3) with the Ki values lower than the unbound plasma concentration of probenecid, indicating the interaction with probenecid includes inhibition of the basolateral uptake process mediated by OAT1 and/or OAT3. 

A procedure for the determination of diuretics of different therapeutical character high (bumetanide, ethacrynic acid, furosemide), intermediate (bendroflumethiazide, chlorthalidone, hydrochlorothiazide, xipamide) and low (acetazolamide, amiloride, spironolactone, triamterene) efficacy diuretics, and the uricosuric agent probenecid, in urine samples, illustrates a method development implying the control of pH, surfactant and modifier [23]. The greatest analytical problems in the detection of these compounds are basically their wide variety of chemical structures, functional groups and protonation constants. This implies the use of several experimental conditions for their analysis with conventional aqueous-organic mobile phases and laborious liquid-liquid or solid-liquid extraction prior to chromatographic separation. In contrast, the same micellar eluent can produce a satisfactory separation after direct injection. 

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