ABSTRACT
Objective To establish a method for rapid screening and quantifying the illegal addition of metolazone in tablet candy by ultra-high performance liquid chromatography-quadrupole-time of flight mass spectrometry(UPLC-Q-TOF/MS).Methods The component in samples was extracted with acetonitrile,then purified by Captiva EMR-Lipid purification column,detected by UPLC-Q-TOF/MS with Agilent RRHD Eclipse Plus C18 chromatographic column(100 mm×2.1 mm,1.8μm)under Targeted MS/MS mode.Results The linear regression analysis data for the calibration plots showed a good linear relationship over the concentration range of 50-1 000 ng·mL-1 for metolazone(r=0.999 0);the value of detection limit and quantification limit was found to be 1.0 μg.g1 and 2.5 μg·g-1.The average recovery rate was 98.15%(RSD=2.2%,n=18).Conclusion The method had the advantages of simple operation,qualitative and quantitative accuracy.It could be applied to daily inspection.
ABSTRACT
Objective To establish an HPLC method to determine the related substances of metolazone and valsartan in com?pound metolazone tablets. Methods An Agilent Eclipse SB-C18 column (4.6 mm × 250 mm,5 μm) was used with 0.01 mol/L KH2PO4 buffer(pH=3.5)-acetonitrile as the mobile phase with gradient elution at a flow rate of 1.0 ml/min. The column temperature was 30℃ and the detection wavelength was 237 nm. Injection volume was 20 μl. Results Metolazone,valsartan and related sub?stance B of valsartan were separated completely. The calibration curves were linear within the range of 3-30μg/ml for metolazone, 0.1-2.0μg/ml for valsartan and 0.08-2.0μg/ml for related substane B of valsartan. The average recoveries were 102.97%,100.81%and 100.44%,respectively. The repeatability and intermediate precision met with requirements. The test solution was stable within 24 h. Conclusion The method is specific,sensitive,accurate and reliable,thereby can be used for the determination of metolazone and valsartan related substances in compound metolazone tablets.
ABSTRACT
Objective To establish an HPLC method to determine the related substances of metolazone and valsartan in compound metolazone tablets. Methods An Agilent Eclipse SB-C18 column 4.6 mm × 250 mm, 5 μm was used with 0.01 mol/L KH2PO4 buffer pH=3.5-acetonitrile as the mobile phase with gradient elution at a flow rate of 1.0 ml/min. The column temperature was 30℃ and the detection wavelength was 237 nm. Injection volume was 20 μl. Results Metolazone, valsartan and related substance B of valsartan were separated completely. The calibration curves were linear within the range of 3-30 μg/ml for metolazone, 0.1-2.0 μg/ml for valsartan and 0.08-2.0 μg/ml for related substane B of valsartan. The average recoveries were 102.97%, 100.81% and 100.44%, respectively. The repeatability and intermediate precision met with requirements. The test solution was stable within 24 h. Conclusion The method is specific, sensitive, accurate and reliable, thereby can be used for the determination of metolazone and valsartan related substances in compound metolazone tablets.
ABSTRACT
Objective To develop an LC-MS/MS method for simultaneous determination of metolazone and valsartan in beagle dog plasma.Methods The chromatographic separation was achieved on an Agilent Poroshell 120(2.1 mm ×30 mm × 2.7 μm)analytical column.The multiple reaction monitoring mode operating in positive ion was adopted in MS detection, and precursors to the product ion transitions of m/z 366.2/259, 436.2/291 and 423.4/207 were used to measure metola-zone, valsartan and internal standard ( losartan potassium) .Results The method was linear over the concentration range of 0.5 ng/ml-100 ng/ml for metolazone and 5-5000 ng/ml for valsartan, with the correlation coefficients ( r2 ) of 0.9937 and 0.9939, respectively.The average intra-day precision values ( RSD) were 2.09% -8.85% for metolazone and 2.36%-13.12%for valsartan.The matrix effect values were 87.73%-98.62%for metolazone and 99.03%-137.35%for valsartan.The average recovery was 75.74%-81.82%for metolazone and 83.89%-95.64%for valsartan.Conclu-sion This analytical method for metolazone and valsartan is simple, accurate and sensitive, so it can be used for pharma-cokinetic research of metolazone and valsartan immediate release tablets in beagle dogs.
ABSTRACT
Objective To establish a method for testing the dissolution of valsartan and metolazone tablets, and validate the method to provide a basis for drug quality control. Methods The dissolution was analyzed by HPLC method. An Agilent SB C18 (4.6 mm×250 mm, 5 μm) column and a mixture of acetonitrile and water were used with the ratio of 50: 50 at a flow rate of 1.0 ml/min with UV detection at 235 nm. Results The calibration curve of valsartan and metolazone was 6-120 μg/ml (r=1.0000, n=6) and 37.5-750 ng/ml (r=1.0000, n=6), respectively. The average recovery of the two drugs was 99.85% and 99.44% with RSD of 1.05% and 1.16% (n=9), respectively. The test solution was stable within 24 h and the filter did not interfere with determination as the two drugs were not adsorbed on it. RSD of this method were all less than 2%. Conclusion The method is simple, sensitive, accurate, and with highly distinguished ability for quality control.