Effects of escin on indinavir crystallization time in the urine of patients with HIV-I infection: a multicenter, randomized, open-label, controlled, four-period crossover trial.

BACKGROUND: The combination of indinavir, a protease inhibitor, and reverse-transcriptase inhibitors is widely used in the treatment of HIV-1 infection. However, precipitation of indinavir crystals in the renal tubular lumen due to the drug's aqueous insolubility may result in characteristic symptoms of flank pain or classic renal colic. An in vitro study has shown that addition of escin to synthetic urine containing indinavir delayed the crystallization time of indinavir. OBJECTIVE: This study examined the efficacy and tolerability of the addition of escin to highly active antiretroviral therapy containing indinavir to delay the crystallization time of indinavir in urine. METHODS: This was a multicenter, randomized, open-label, controlled, 4-period crossover trial in which each period lasted 4 weeks. HIV-1-infected adults receiving treatment with indinavir plus 2 nucleoside analogue reverse-transcriptase inhibitors in whom plasma viral loads had been undetectable (HIV-1 RNA <200 copies/mL) for at least 6 months were randomly assigned to 1 of 2 groups based on the timing of the initiation of escin. Group I received escin during the second and third treatment periods, and group II received escin during the first and fourth treatment periods. The primary end point was the in vitro crystallization time of indinavir in 24-hour urine specimens, determined at the end of each 4-week period. Tolerability was assessed based on the number of patients with a rebound in plasma viral load and on the numbers of clinically and biologically relevant adverse events (including those requiring discontinuation of treatment). Clinical and laboratory evaluations were performed throughout each 4-week period. RESULTS: Fifty HIV-1-infected patients were enrolled, 47 were randomized to treatment (40 [85.1%] men, 7 [14.9%] women; median [interquartile range] age, 36 [34-45] years), and 30 completed the study. Urine pH and plasma and urine indinavir concentrations were unaffected by the addition of escin to antiretroviral treatment. The mean time to the onset of crystallization was 14.7 minutes with escin (95% Cl, 11.8-17.5) and 9.9 minutes without it (95% Cl, 6.7-13.1). Therefore, the addition of escin increased the mean crystallization time by 5.5 minutes (95% Cl, 1.5-9.5; P = 0.008), representing the overall capacity of study treatment to inhibit indinavir crystallization in the urine. Three of 47 patients had mild gastrointestinal symptoms associated with escin treatment. No episodes of nephrolithiasis were recorded during the study or after the completion of study treatment. CONCLUSION: The results of this prospective clinical trial of the effect of escin on indinavir crystallization time support the possibility that indinavir-associated nephrolithiasis may be prevented by means other than overhydration. Further research is needed in greater numbers of patients over longer follow-up times.

Bead-injection determination of total mercury in river water samples.

A bead-injection system is proposed for total mercury determination in river-water samples. The procedure is based on the introduction of a defined quantity of a resin suspension in the flow system. The selected beads are packed inside of a flow cell and the formed resin mini-column constitutes the optical path. The sample volume is then selected, and its passage by the mini-column allows retention of the mercury ions on the surfaces of the beads. The introduction of a spectrophotometric reagent in the flow system leads to the formation of a colored Hg-dithizone complex on the surface of the bead, which is spectrophotometricaly monitored. The spent beads are directed to waste, allowing the system to become ready to process another sample. The proposed system handles about 20 measurements per hour, consuming 1000 microl of the sample, 1 mg of Chelex 100 resin and 1.25 microg of Dithizone per determination. When 1000 microl of the sample is injected, a linear analytical curve is obtained (A = 0.0052[Hg] + 0.1028, from 0 up to 30 microg l(-1), R2 = 0.995); the detection limit is estimated to be 0.9 microg l(-1). The results are precise, r.s.d. < 9%; spiked sample recoveries within 91.2 and 109% are found.

A new strategy for exploiting ion exchange in sequential injection analysis: in-line phytic acid separation/determination in foods as an example.

A novel strategy for exploiting ion exchange in sequential injection systems is proposed. The procedure is based on the selection of a defined volume of a resin suspension, which is introduced and packed in the analytical path, establishing a resin mini-column in the system. The passage of a selected sample volume through the resin mini-column leads to the retention of the analyte, while the sample matrix is discarded. The analyte is eluted during the passage of the eluant/reagent by the packed beads, being the analytical signal monitored (absorbance) in the liquid phase. The beads are then aspirated back to the holding coil and directed to a recovery flask, linked at the selection valve; then the system is ready to begin a new cycle. With the proposed strategy, the main characteristics of the sequential injection system are kept as any new artifact is added to the manifold and system reconfiguration is not required. The feasibility of the approach is demonstrated by the phytic acid determination in food samples. For this specific application, AG1-X8 was selected as ion exchanger, and a solution containing Cl- and Fe(III)-salicylate complex was used as eluant and spectrophotometric reagent.