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Journal of Chromatographic Science Apr 2020Two robust and selective stability-indicating chromatographic methods were developed and validated for the determination of metolazone in drug substance and...
Development and Validation of Two Robust Stability-Indicating Chromatographic Methods for Determination of Metolazone in Drug Substance and Pharmaceutical Dosage Form in the Presence of Its Degradation Products and Characterization of Main Degradation Products Based on LC-MS.
Two robust and selective stability-indicating chromatographic methods were developed and validated for the determination of metolazone in drug substance and pharmaceutical dosage form in the presence of its degradation products. The HPLC method employed a Kromasil C18 (250 × 4.6,5 μm) column and a mobile phase of acetonitrile: 0.2% orthophosphoric acid (32:68 v/v) at a flow rate 2 mL/min and detection at 238 nm. The separation was performed in HPLC isocratic mode. The robustness of the suggested method was assessed using the Plackett-Burman design, parameters affecting system suitability were established and non-significant intervals for the significant parameters were considered. The HPTLC method employed Nano-SIL-20 UV254 HPTLC plates as adsorbent, ethyl acetate: toluene: acetic acid solution (4:4:0.5, v/v/v), as a developing solvent system and densitometric detection at 238 nm. Metolazone was exposed to different stress conditions, including acid and alkaline hydrolysis and oxidative and photolytic degradation. The main degradation products obtained have been characterized and interpreted based on LC-MS. The linearity of the suggested methods was proved in the concentration range of 20-75 μg/mL for the HPLC method and 100-900 ng/spot for the HPTLC method. The suggested methods were validated according to international conference on harmonization guidelines. These methods were successfully dedicated for the estimation of metolazone in drug substance and pharmaceutical dosage form in the presence of its degradation products. The results of the suggested methods were evaluated and compared statistically with results obtained by an official method without finding any significant difference.
Topics: Calibration; Chromatography, High Pressure Liquid; Chromatography, Reverse-Phase; Chromatography, Thin Layer; Drug Stability; Hydrolysis; Mass Spectrometry; Metolazone; Tablets
PubMed: 31879759
DOI: 10.1093/chromsci/bmz110 -
The Annals of Pharmacotherapy Apr 2017In cases of loop diuretic resistance in the intensive care unit (ICU), recommendations for a specific second-line thiazide agent are lacking.
BACKGROUND
In cases of loop diuretic resistance in the intensive care unit (ICU), recommendations for a specific second-line thiazide agent are lacking.
OBJECTIVE
To compare the effects of intravenous chlorothiazide (CTZ) and enteral metolazone (MET) on urine output (UOP) when added to furosemide monotherapy therapy in critically ill adults.
METHODS
This was a retrospective cohort study conducted in the medical, surgical, and cardiothoracic ICUs of a quaternary medical center. The primary outcome was change in UOP induced by the study interventions compared with furosemide alone. Secondary outcomes included onset of diuresis, eventual need for hemodialysis, and incidence of adverse events.
RESULTS
A total of 122 patients (58 in CTZ, 64 in MET) were included. When added to furosemide monotherapy, CTZ induced a greater change in UOP at 24 hours compared with MET (2405 vs 1646 mL, respectively; P = 0.01). CTZ also caused a more rapid dieresis: 1463 mL total UOP in the first 6 hours compared with 796 mL in the MET group ( P < 0.01). There were no differences found regarding ICU length of stay, need for renal replacement therapy, or survival to discharge. The CTZ arm required more potassium supplementation to maintain normokalemia (median 100 vs 57 mEq in MET; P = 0.02) and carried a higher cost (mean $97 vs $8, P < 0.01).
CONCLUSION
Both CTZ and MET induced significant increases in UOP. CTZ induced a greater and more rapid change and was associated with higher cost and greater need for potassium replacement. Randomized controlled trials are needed to establish whether a preferable thiazide diuretic exists in this setting.
Topics: Administration, Intravenous; Administration, Oral; Adult; Chlorothiazide; Critical Illness; Diuresis; Drug Therapy, Combination; Female; Furosemide; Humans; Intensive Care Units; Male; Metolazone; Retrospective Studies; Sodium Potassium Chloride Symporter Inhibitors
PubMed: 28228057
DOI: 10.1177/1060028016683971 -
JPMA. the Journal of the Pakistan... Dec 2019To compare efficacy and safety of indapamide-furosemide combination against metolazone-furosemide combination in refractory heart failure patients. (Randomized Controlled Trial)
Randomized Controlled Trial
Comparing the sodium excreting efficacy of furosemide and indapamide combination against furosemide and metolazone combination in congestive heart failure patients: A randomized control trial.
OBJECTIVE
To compare efficacy and safety of indapamide-furosemide combination against metolazone-furosemide combination in refractory heart failure patients.
METHODS
The randomised controlled trial was conducted at Rehman Medical Institute, Peshawar, Pakistan, from January 1 to June 30, 2018, and comprised refractory heart failure patients who were randomised into two groups using lottery method Group 1 received intravenous furosemide 40mg Q12hr with metolazone 5mg Q24hr, while group 2 received intravenous furosemide 40mg Q12hr with indapamide 2.5mg Q24hr. Both groups were assessed for urinary sodium excretion, total urine output and decrease in weight on day one, day three and day five of admission. SPSS 22 was used for data analysis.
RESULTS
Of the 150 patients, there were 75(50%) in each of the two groups. Mean age in group 1 was 64.8}11.2 years, while it was 66.3}12.9 years in group 2. Both groups showed increased urinary sodium excretion and total urine output (p>0.05). Hypokalaemia was the most common adverse event 66%. Mean hospital stay was not significantly different between the groups (p>0.05).
CONCLUSIONS
There was no significant differences between adverse events and efficacy between patients receiving either indapamide-furosemide combination or metolazone-furosemide combination.
Topics: Administration, Intravenous; Administration, Oral; Aged; Body Weight; Diuretics; Drug Therapy, Combination; Female; Furosemide; Heart Failure; Humans; Indapamide; Male; Metolazone; Middle Aged; Pakistan; Sodium
PubMed: 31853105
DOI: 10.5455/JPMA.3401 -
British Medical Journal (Clinical... May 1981
Topics: Aged; Diuretics; Drug Synergism; Edema; Humans; Male; Metolazone; Middle Aged; Potassium; Sodium
PubMed: 6784852
DOI: 10.1136/bmj.282.6274.1432 -
Current Therapeutic Research, Clinical... Dec 1976
Topics: Administration, Oral; Adult; Antihypertensive Agents; Blood Pressure; Cholesterol; Depression, Chemical; Diuretics; Drug Administration Schedule; Drug Evaluation; Drug Therapy, Combination; Humans; Hypertension; Male; Metolazone; Middle Aged
PubMed: 827420
DOI: No ID Found -
The New England Journal of Medicine Sep 1998
Topics: Child; Diuretics; Drug Therapy, Combination; Furosemide; Humans; Infant; Metolazone; Nephrotic Syndrome
PubMed: 9742030
DOI: 10.1056/NEJM199809103391115 -
Journal of Clinical Pharmacology 1973
Clinical Trial
Topics: Adult; Aged; Blood Pressure; Body Weight; Clinical Trials as Topic; Creatinine; Diuretics; Edema; Female; Glomerular Filtration Rate; Graft Rejection; Humans; Ketones; Kidney; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Nephrotic Syndrome; Potassium; Quinazolines; Sulfonamides; Transplantation, Homologous; Uric Acid
PubMed: 4579972
DOI: 10.1002/j.1552-4604.1973.tb00224.x -
Postgraduate Medical Journal Dec 1971The use of metolazone (Zaroxolyn), a new diuretic, in fifty-two African patients is described. The drug was found to be safe and moderately effective when used alone,...
The use of metolazone (Zaroxolyn), a new diuretic, in fifty-two African patients is described. The drug was found to be safe and moderately effective when used alone, but combined with frusemide it proved to be of great value in patients whose fluid retention was refractory to other diuretics.
Topics: Adult; Black People; Body Weight; Diuretics; Drug Synergism; Edema; Female; Furosemide; Humans; Ketones; Male; Middle Aged; Quinazolines; Sulfonamides
PubMed: 5138749
DOI: 10.1136/pgmj.47.554.789 -
Arzneimittel-Forschung Jan 1975The solubility and dissolution rate of five different solid forms of 7-chloro-1,2,3,4-tetrahydro-2-methyl-4-oxo-o-tolyl-6-quinazoline-sulfonamide (metolazone) in...
The solubility and dissolution rate of five different solid forms of 7-chloro-1,2,3,4-tetrahydro-2-methyl-4-oxo-o-tolyl-6-quinazoline-sulfonamide (metolazone) in n-butanol, water and 0.01 n HCl are investigated and thermodynamic values have been computed. The amorphous metolazone dissolves about 8 times faster than the stable modification I (mp. 267-270 degrees C) in 0.01 n HCl at 37 degrees C.
Topics: Butanols; Chemical Phenomena; Chemistry, Physical; Diuretics; Metolazone; Solubility; Thermodynamics; Time Factors; Water
PubMed: 1173767
DOI: No ID Found -
Israel Journal of Medical Sciences Nov 1986Ten patients with severe congestive heart failure (6 women and 4 men, aged 67 +/- 4.35 years) were given diuretic therapy with either furosemide or metolazone followed...
Ten patients with severe congestive heart failure (6 women and 4 men, aged 67 +/- 4.35 years) were given diuretic therapy with either furosemide or metolazone followed by combined therapy of both agents. We found that the furosemide-metolazone combination induced greater natriuresis, urinary output and weight loss than did furosemide or metolazone alone. Notably, none of our patients displayed profound diuresis, severe hyponatremia or deterioration of renal function, found previously in high-risk patients treated with this combination.
Topics: Aged; Body Weight; Diuretics; Drug Therapy, Combination; Female; Furosemide; Heart Failure; Humans; Male; Metolazone; Middle Aged; Potassium; Sodium; Water-Electrolyte Balance
PubMed: 3793436
DOI: No ID Found