Effect of the location of hydrogen abstraction on the fragmentation of diuretics in negative electrospray ionization mass spectrometry.
The diuretic agents bumetanide, xipamide, indapamide, and related compounds were investigated in order to determine the effect of different ionization sites on their collisionally activated dissociation and the corresponding fragmentation pathways. Therefore, analytes were selectively alkylated, and structural analogues as well as deuterium labeled compounds synthesized, which contain a reduced number of ionizable hydrogen atoms. Thus, specific hydrogen abstractions and their correlated dissociation routes of the negatively charged molecules were eliminated, providing evidence for the influence of the location of ionization on product ion spectra. Fragment ions such as m/z 78 indicate ionization at the commonly present sulfamoyl residue of diuretics but does not exclude additional ionization sites. Product ion spectra of the investigated diuretic agents proved to be composed by fragmentations initiated from different hydrogen abstractions. Moreover, the generation of radical anions by collision-activated dissociation of even-electron precursor ions was observed, the generation of which is discussed by proposed fragmentation pathways. (+info)
Experimental design optimization of a capillary zone electrophoresis method for the screening of several diuretics and ACE inhibitors.
Experimental design methodologies are applied to the development of a capillary zone electrophoretic method for the separation of the angiotensin-converting enzyme inhibitor enalapril and its derivative enalaprilat and the diuretics xipamide and hydrochlorothiazide. The effects of pH, buffer concentration, proportion of boric acid in the mixed boric acid-potassium dihydrogen phosphate background electrolyte, temperature, applied voltage, and percentage of organic modifier are studied. Critical factors are identified in a screening design (a 2(6-2) fractional factorial design), and afterwards, optimal conditions for the separation are reached by means of an optimization design (a 2(2) + 2 x 2 + k central composite design). The studied response is the resolution between peaks. The four studied compounds can be separated in less than 3.5 min using an electrolyte of 20mM boric acid-potassium dihydrogen phosphate (75:25, v/v) with 5% MeOH adjusted to pH 8.0 with KOH, at a potential of 30 kV. The detection wavelength and temperature are 206 nm and 35 degrees C, respectively. (+info)
Once daily treatment of mild to moderate hypertension with xipamid: a controlled study.
A double-blind, placebo controlled, crossover trial of 20 and 40 mg of xipamid once daily in the treatment of mild to moderate hypertension is reported and some of the difficulties and pitfalls of multicentre trials of this type are described. 2 Both doses were significantly more effective in reducing the blood pressure than the placebo and neither was superior to the other. Both produced some potassium loss. Xipamid acted for at least 22 h and was effective in up to 83% of the patients. 3 Further trials are suggested to investigate the activity of a lower dose than 20 mg. (+info)
Xipamide: no advantage over bendrofluazide in hypertension.
In patients with uncontrolled hypertension addition of xipamide 20 mg daily to bendrofluazide 5 mg daily produced no significant additive antihypertensive effect, and the 95% confidence limits excluded a clinically important response. Xipamide treatment worsened hypokalaemia and increased the blood urea concentration significantly. (+info)
Xipamide and cyclopenthiazide in essential hypertension--comparative effects on blood pressure and plasma potassium.
1 The blood pressure lowering effect of xipamide, a non-thiazide diuretic given for 6 weeks was compared in a randomised cross-over trial with that of cyclopenthiazide in 14 patients with essential hypertension. 2 Xipamide 10 or 20 mg given once daily was as effective in lowering supine blood pressure as daily cyclopenthiazide 0.5 mg. There was no difference in the blood pressure lowering effect of 10 mg xipamide daily for 2 weeks compared to 20 mg daily given for a further 4 weeks. 3 Plasma potassium was reduced by both drugs, but markedly more after both 10 mg and 20 mg xipamide than after cyclopenthiazide 0.5 mg. By the sixth week of treatment 13 of 14 patients on xipamide but only 6 of 14 on cyclopenthiazide has plasma potassium concentrations of, or less than, 3.5 mmol/l. The fall in plasma potassium was significantly greater and the final plasma potassium concentration was significantly lower after either dose of xipamide than after cyclopenthiazide. 4 These results suggest that 10 mg or 20 mg of xipamide daily is effective in lowering blood pressure in hypertensive patients but is associated with hypokalaemia. In view of recent evidence linking diuretic-induced hypokalaemia with cardiac dysrhythmias in patients with essential hypertension we would suggest that thiazide diuretics be used in preference to xipamide for the routine management of essential hypertension. Our results also suggest that the currently recommended dose of xipamide (20 mg) for the treatment of hypertension is excessive, and lower amounts than 10 mg per day might possibly be as effective in lowering blood pressure with less adverse metabolic consequences. (+info)
A study of the antihypertensive action of xipamide using ambulatory intra-arterial monitoring.
1 The antihypertensive activity of the diuretic xipamide has been studied in 18 patients with mild/moderate essential hypertension using the technique of continuous ambulatory intra-arterial blood pressure recording. Full data from 48 h blood pressure recordings before and after treatment were available from 13 patients. 2 After a mean period of 3 months' treatment with xipamide 20 mg once daily, both systolic and diastolic blood pressure were markedly reduced throughout the whole 24 h day, the reductions of systolic being statistically significant throughout the whole period, and of diastolic for 19 out of the 24 hourly periods measured. There was no postural hypotension seen during treatment and there was a conspicuous lack of side effects. 3 Xipamide would appear to be as effective as many beta-adrenoceptor blockers but without their side effects and produces a better control of blood pressure throughout the whole day and night. (+info)