Limited information indicates that maternal doses of probenecid up to 2 grams daily produce low levels in milk and would not be expected to cause any adverse effects in breastfed infants, especially if the infant is older than 2 months. In animal studies, probenecid increased the breastmilk excretion of cimetidine, possible via an interaction with an active transport mechanism in the breast.[1] The implications of enhanced excretion of drugs given with probenecid for nursing mothers and their infants has not been studied; however, only a few drugs are known to undergo active transport into breastmilk.

Two stability-indicating chromatographic methods have been established and validated for concurrent determination of probenecid (PRO), colchicine (COL) along with the degradation product of colchicine (COL deg). PRO and COL were exposed to a stress stability study, which includes acidic, alkaline, oxidative, photolytic and thermal degradations. Chromatographic methods included the use of thin layer chromatography (TLC-densitometry) and high performance liquid chromatography (HPLC). In the first method, separation was achieved by using aluminum TLC plates that were precoated with silica gel G.F254 as the stationary phase and ethyl acetate-methanol-33%ammonia (8:1:1, by volume) as a mobile phase. The obtained chromatograms were scanned at 254 nm. The second method was based on HPLC using a RP- C18 column with isocratic elution. Good separation was obtained through a mobile phase comprised of phosphate buffer pH 5-acetonitrile (70:30, v/v) at a flow rate of 1.0 mL min-1 and ultraviolet detection at 254 nm. Different parameters affecting efficiency of the two methods were studied accurately for optimum separation of the three cited components. The suggested methods were validated according to the International Conference on Harmonization (ICH) guidelines and were applied for bulk powder and commercial tablets.

We presented an update in the field of hypouricemia, which is defined as a serum urate concentration of < 2 mg/dL (119 μmol/L), for the practicing rheumatologist, who usually is the consulting physician in cases of disorders of urate metabolism. We performed a narrative review through a literature search for original and review articles in the field of human hypouricemia published between January 1950 and July 2018. We divided the etiology of hypouricemia into two main categories: those associated with a decrease in urate production and those promoting the elimination of urate via the kidneys. The most common conditions associated with these categories are discussed. Furthermore, the etiology of hypouricemia may be associated with certain medications prescribed by the practicing rheumatologists, such as the following: urate-lowering drugs (allopurinol and febuxostat); recombinant uricase (pegloticase); uricosuric agents (probenecid, benzbromarone); urate transporter URAT1 inhibitor (lesinurad); angiotensin II receptor blocker (losartan); fenofibrate; high-dose trimethoprim-sulfamethoxazole; some NSAID; and high-dose salicylate therapy. The rheumatologist is considered an expert in the metabolism of urate and its associated pathological conditions. Therefore, specialists must recognize hypouricemia as a biomarker of various pathological and potentially harmful conditions, highlighting the importance of conducting a deeper clinical investigation to reach a more accurate diagnosis and treatment.

A simple MEKC method is described for the separation and quantification of seven widely used uricosuric and antigout drugs, including allopurinol (AP), benzbromarone (BZB), colchicine (COL), orotic acid (OA), oxypurinol (OP), probenecid (PB), and sulfinpyrazone (SPZ). The drugs were separated in a BGE of borate buffer (45 mM; pH 9.00) with SDS (20 mM) as the micellar source and the separated drugs were directly monitored with a UV detector (214 nm). Several parameters affecting the separation and analysis of the drugs were studied. Based on the normalized peak-area ratios of the drugs to an internal standard versus the concentration of the drugs, the method is applicable to quantify BZB, COL, and SPZ (each 5-200 microM), AP, OA, OP, and PB (each 10-200 microM) with detection limits (S/N = 3, 0.5 psi, 5 s injection) in the range of 0.6-4.0 microM. The precision (RSD; n = 5) and accuracy (relative error; n = 5) of the method for intraday and interday analyses of the analytes at three levels (30, 120, and 180 microM) are below 4% (n = 3). The method was demonstrated to be suitable for the analysis of AP and COL in commercial tablets with speed and simplicity.