Two liquid chromatographic approaches for the simultaneous determination of xipamide and its degradation product (2,6-xylidine) using time-programmed fluorescence detection.

A study of the performance of reversed-phase chromatography with a programmable multiwavelength fluorimetric technique using either conventional hydro-organic or micellar eluent is established for the determination of xipamide (XIP) in the presence of its degradation product, 2,6-xylidine (XY). In conventional liquid chromatography (CLC), the analyses were carried out on a Promosil ODS 100 Å column (250 mm × 4.6 mm i.d., 5 µm) using a mobile phase consisting of methanol/0.1 M phosphate buffer (65: 35, v/v) at pH 4.0. For micellar liquid chromatography (MLC), a short Spherisorb column (150 mm × 4.6 mm i.d., 5 µm) was employed in conjunction with a greener mobile phase (pH 5.0) containing 0.1 M sodium dodecyl sulfate and 15% n-propanol. CLC proved to be superior to MLC in terms of sensitivity for the determination of the degradation product because it could detect trace amounts down to 10.0 ng/ml of XY as a degradation product in XIP. However, MLC represents an eco-friendly approach for the simultaneous determination of XIP and XY. In addition, the opportunity for the direct introduction of biological matrices into the chromatographic system is one of the distinctive benefits of MLC. The proposed methods were applied for the determination of XIP in its tablets, human urine and content uniformity testing. The results of the proposed methods were statistically compared with those obtained using the comparison fluorimetric method, revealing no significant differences in the performance of the methods regarding accuracy and precision.

Xipamide. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy.

Xipamide is a diuretic derived from salicylic acid and has a structural resemblance to chlorthalidone. Its pharmacodynamic profile shows a diuretic efficacy is similar to that of frusemide (furosemide) at doses up to 40 mg, but the onset and duration of action are comparable to those of hydrochlorothiazide. Xipamide has been studied mostly in the treatment of mild to moderate essential hypertension, with few controlled studies of its use in oedematous states. The efficacy of xipamide 20 to 40 mg once daily in patients with mild to moderate hypertension is comparable to that of bendrofluazide 5 mg, bumetanide 1 mg or hydrochlorothiazide 50 mg when used alone in newly treated or previously treated patients. The addition of xipamide 20 to 40 mg daily to regimens containing beta-blockers, adrenergic neuron-blocking drugs and/or methyldopa has resulted in a further reduction in blood pressure. A few studies in oedematous states suggest that xipamide 40 to 80 mg is comparable in efficacy to equal doses of frusemide, and that the side effects of hypokalaemia, hyperuricaemia and increased blood glucose in diabetics or latent diabetics are similar to those of other diuretics. Thus, xipamide is a suitable alternative to other diuretics in the treatment of mild to moderate hypertension and combines the efficacy of frusemide with a less abrupt action in the treatment of oedema.

Pharmacodynamics and pharmacokinetics of xipamide in patients with normal and impaired kidney function.

The effect of a single oral dose of 40 mg xipamide on urinary excretion of Na+, K+, Cl-, Ca2+ and Mg2+ in healthy subjects and in patients with varying degrees of renal impairment was compared with various conventional diuretics. Xipamide caused marked excretion of Na+ and Cl-, whereas the diuretic produced only moderate kaliuresis; urinary excretion of Ca2+ was increased in proportion to Na+, like the loop diuretics. Xipamide affected electrolyte excretion even in patients with a creatinine clearance below 30 ml/min, as do the loop diuretics, too. Therefore, the pharmacodynamic characteristics of xipamide are more like those of a loop diuretic than of a thiazide. Xipamide was good bioavailable, its t 1/2 beta was 7 h and urinary recovery of the undegraded drug was 40% of the given dose. In renal insufficiency, t 1/2 beta increased from 7 to only 9h, yielding a moderate increase in the AUC. Urinary recovery of the drug was reduced in proportion to the reduction in the creatinine clearance of the patient. Therefore, significant extrarenal elimination of the diuretic must be postulated, which suffices to prevent significant drug accumulation in renal failure.

[Pharmacokinetics of xipamide and triamterene in healthy probands]. / Pharmakokinetik von Xipamid und Triamteren bei gesunden Probanden.

Simultaneous detection of 4-chloro-5-sulfamoyl-2',6'-salicyl-oxylidide (Xipamide) and 2,4,7-triamino-6-phenyl-pteridine (Triamterene) in urine specimen of healthy volunteers was achieved by means of a new high performance liquid chromatography (HPLC) method. Pharmacokinetics of both substances in combination (Neotri, dose ratio xipamide: triamterene = 1:3) did not significantly differ from those of the sole substances. Peak urine elimination of unaltered xipamide was 2.5 +/- 0.7 mg/h when given alone and 2.0 +/- 0.7 mg/h in the presence of triamterene. The data for the triamterene excretion were 0.7 +/- 0.1 mg/h and 1.0 +/- 0.3 mg/h, respectively within 1-3 h post application. Assuming a two-compartment pharmacokinetic model the terminal elimination half-lives of unchanged xipamide were 5.3 +/- 1.9 h (monosubstance) and 4.0 +/- 0.6 h (combination). The corresponding data for unchanged triamterene were 6.4 +/- 1.3 h (monosubstance) and 5.5 +/- 1.8 h (combination).