Method development and validation of the simultaneous determination of a novel topoisomerase 1 inhibitor, the prodrug, and the active metabolite in human plasma using column-switching LC–MS/MS, and its application in a clinical trial

2011 ◽  
Vol 879 (30) ◽  
pp. 3415-3422 ◽  
Author(s):  
Tomonori Kamei ◽  
Takahide Uchimura ◽  
Kazuhiro Nishimiya ◽  
Takehiko Kawanishi
Keyword(s):  
Clinical Trial ◽  
Simultaneous Determination ◽  
Human Plasma ◽  
Active Metabolite ◽  
Method Development ◽  
Column Switching ◽  
Topoisomerase 1 ◽  
Method Development And Validation ◽  
Development And Validation

scholarly journals A HPLC-MS/MS METHOD DEVELOPMENT AND VALIDATION FOR THE SIMULTANEOUS DETERMINATION OF NIFEDIPINE AND ENALAPRIL IN HUMAN PLASMA

2018 ◽  
Vol 10 (4) ◽  
pp. 35 ◽  
Author(s):  
Liliya Logoyda
Keyword(s):  
Formic Acid ◽  
Simultaneous Determination ◽  
Human Plasma ◽  
Method Development ◽  
Accurate Method ◽  
Sample Volume ◽  
Ich Guidelines ◽  
Method Development And Validation ◽  
Development And Validation

Objective: The main purpose of this study was to develop a simple, precise, rapid and accurate method for the simultaneous quantification of nifedipine and enalapril in human plasma.Methods: Chromatography was achieved on Discovery C18, 50 × 2.1 mm, 5 μm column. Samples were chromatographed in a gradient mode (eluent A (acetonitrile-water–formic acid, 5: 95: 0.1 v/v), eluent B (acetonitrile–formic acid, 100: 0.1 v/v)). The initial content of the eluent B is 0%, which increases linearly by 1.0 min to 100% and to 1.01 min returns to the initial 0%. The mobile phase was delivered at a flow rate of 0.400 ml/min into the mass spectrometer ESI chamber. The sample volume was 5 μl.Results: The total chromatographic run time was 2.5 min and the elution of nifedipine, enalapril and IS (verapamil) occurred at ~1.83, 1.57 and 1.61 min, respectively. A linear response function was established at 1-100 ng/ml for nifedipine and 2-200 ng/ml for enalapril maleate in human plasma. The % mean recovery for enalapril in LQC, MQC and HQC was 114.0 %, 112.9 % and 113.2 %, for nifedipine in LQC, MQC and HQC was 104.1 %, 105.0 % and 108.7 % respectively. The lowest concentration with the RSD<20% was taken as LLOQ and was found to be 2.16 ng/ml for enalapril, 1.01 ng/ml for nifedipine. The % accuracy of LLOQ samples prepared with the different biological matrix lots was found 108.2 % for enalapril and 100.5 % for nifedipine, which were found within the range of 80.00-120.00 % for the seven different plasma lots. % CV for LLOQ samples was observed as 3.2 % and 7.4 % respectively, which are within 20.00% of the acceptance criteria.Conclusion: A rapid method was developed for simultaneous determination of nifedipine and enalapril in human plasma. The method was strictly validated according to the ICH guidelines. Acquired results demonstrate that proposed strategy can be effortlessly and advantageously applied for routine examination of nifedipine and enalapril in human plasma. 

scholarly journals A HPLC-MS/MS METHOD DEVELOPMENT AND VALIDATION FOR THE SIMULTANEOUS DETERMINATION OF BISOPROLOL AND ENALAPRIL IN THE PRESENT OF ENALAPRILAT IN HUMAN PLASMA

2018 ◽  
Vol 10 (2) ◽  
pp. 31 ◽  
Author(s):  
Liliya Logoyda ◽  
Dmytro Korobko ◽  
Oleksandra Oleshchuk ◽  
Taras Proniv ◽  
Mariya Dmutriv
Keyword(s):  
Formic Acid ◽  
Simultaneous Determination ◽  
Human Plasma ◽  
Method Development ◽  
Sample Volume ◽  
Ich Guidelines ◽  
Method Development And Validation ◽  
Initial Content ◽  
Development And Validation

Objective: A highly specific, sensitive and rapid HPLC-MS/MS method has been developed and validated for the simultaneous quantification of bisoprolol and enalapril in the present of enalaprilat in human plasma.Methods: Analytes were extracted from plasma using a protein precipitation extraction method. Chromatography was achieved on Discovery C18, 50 × 2.1 mm, 5 μm column. Samples were chromatographed in a gradient mode (eluent A (acetonitrile-water–formic acid, 5: 95: 0.1 v/v), eluent B (acetonitrile–formic acid, 100: 0.1 v/v)). The initial content of the eluent B is 0%, which increases linearly by 1.0 min to 100% and to 1.01 min returns to the initial 0%. The mobile phase was delivered at a flow rate of 0.400 ml/min into the mass spectrometer ESI chamber. The sample volume was 5 μl.Results: The total chromatographic run time was 2.0 min and the elution of bisoprolol, enalapril, enalaprilat and IS (verapamil) occurred at ~1.01, 1.03, 0.96 and 1.09 min, respectively. A linear response function was established at 0.5-50 ng/ml for bisoprolol fumarate, 2-200 ng/ml for enalapril maleate, 1-100 ng/ml for enalaprilat dehydrate in human plasma. The intraday and interday accuracy and precisions were in the range of 0.311 %-0.647 % and 0.364 %-0.572 % for bisoprolol, 0.321 %-0.747 % and 0.390 %-0.673 % for enalapril, 0.221 %-0.547 % and 0.264 %-0.773 % for enalaprilat, respectively.Conclusion: A new rapid method was developed for simultaneous determination of bisoprolol and enalapril in the present of enalaprilat in human plasma. The method was strictly validated according to the ICH guidelines. The information thus obtained from the study can be used for the full pharmacokinetic profiling in individuals. 

scholarly journals LC-MS/MS METHOD DEVELOPMENT AND VALIDATION FOR THE DETERMINATION OF CARDIAZOL IN HUMAN PLASMA

2019 ◽  
pp. 380-385
Author(s):  
IRYNA DRAPAK ◽  
BORYS ZIMENKOVSKY ◽  
LINA PEREKHODA ◽  
SERGIY KOVALENKO ◽  
Liliya Logoyda
Keyword(s):  
Formic Acid ◽  
Human Plasma ◽  
Method Development ◽  
Accurate Method ◽  
Sample Volume ◽  
Ich Guidelines ◽  
Coefficients Of Variation ◽  
Method Development And Validation ◽  
Development And Validation

Objective: The main purpose of this study was to develop a simple, precise, rapid and accurate method for the quantification of cardiazol in human plasma. Methods: Chromatography was achieved on Discovery C18, 50 × 2.1 mm, 5 μm column. Samples were chromatographed in a gradient mode (eluent A (acetonitrile-water–formic acid, 5: 95: 0.1 v/v), eluent B (acetonitrile–formic acid, 100: 0.1 v/v)). The initial content of the eluent B of 8%, which increases linearly to 1.0 min to 100%, is maintained up to 1.5 min and returned to the original 8% to 1.51 min. The mobile phase was delivered at a flow rate of 0.400 ml/min into the mass spectrometer ESI chamber. The sample volume was 300 μl. Results: The total chromatographic run time was 2.5 min and the elution of cardiazol and IS (difenoconazole) occurred at ~2.15 and 1.98 min, respectively. A linear response function was established at 1-100 ng/ml for cardiazol and difenoconazole in human plasma. The % mean recovery for cardiazol in LQC, MQC and HQC was 102.8 %, 100.3 % and 95.9 %. The lowest concentration with the RSD<20% was taken as LLOQ and was found to be 1.10 ng/ml for cardiazol. The % accuracy of LLOQ samples prepared with the different biological matrix lots was found 109.7 %, which were found within the range of 80.00-120.00 % for the seven different plasma lots. % CV for LLOQ samples was observed as 11.9 %, which are within 20.00% of the acceptance criteria. The within-run coefficients of variation ranged between 0.311 % and 0.601 % for cardiazol. The within-run percentages of nominal concentrations ranged between 99.80 % and 100.41 % for cardiazol. The between-run coefficients of variation ranged between 0.332 % and 0.615 % for cardiazol. The between-run percentages of nominal concentrations ranged between 98.18 % and 101.21 % for cardiazol. Conclusion: A rapid method was developed for simultaneous determination of cardiazol in human plasma. The method was strictly validated according to the ICH guidelines. Acquired results demonstrate that the proposed strategy can be effortlessly and advantageously applied for routine examination of cardiazol in human plasma.

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