Limits...
Development and Validation of a LC-MS/MS Method for the Simultaneous Estimation of Amlodipine and Valsartan in Human Plasma: Application to a Bioequivalence Study.

Jangala H, Vats P, Khuroo AH, Monif T - Sci Pharm (2014)

Bottom Line: The assay was found to be linear over the range of 0.302-20.725 ng/mL for amlodipine and 6.062-18060.792 ng/mL for valsartan.The method was successfully applied for the bioequivalence study of amlodipine and valsartan after oral administration of a fixed dose of the combination.Additionally, as required by the current regulatory bodies, incurred sample reanalysis was performed and found to be acceptable.

View Article: PubMed Central - PubMed

Affiliation: Clinical Pharmacology and Pharmacokinetics, Ranbaxy Research Laboratories, Gurgaon, India.

ABSTRACT
A reliable, simple, and robust liquid chromatography-tandem mass spectro-metric (LC-MS/MS) method has been developed and validated that employs solid-phase extraction for the simultaneous estimation of amlodipine and valsartan in human K3EDTA plasma using amlodipine-d4 and valsartan-d9 as internal standards. Chromatographic separation of amlodipine and valsartan was achieved on the Luna C18 (2)100A (150 × 4.6 mm, 5 μm) column using acetonitrile: 5 mM ammonium formate solution (80:20, v/v) as the mobile phase at a flow rate of 0.8 mL/min in isocratic mode. Quantification was achieved using an electrospray ion interface operating in positive mode, under multiple reaction monitoring (MRM) conditions. The assay was found to be linear over the range of 0.302-20.725 ng/mL for amlodipine and 6.062-18060.792 ng/mL for valsartan. The method has shown good reproducibility, as intra- and interday precisions were within 10% and accuracies were within 8% of nominal values for both analytes. The method was successfully applied for the bioequivalence study of amlodipine and valsartan after oral administration of a fixed dose of the combination. Additionally, as required by the current regulatory bodies, incurred sample reanalysis was performed and found to be acceptable.

No MeSH data available.


Related in: MedlinePlus

Product ion scans of amlodipine and valsartan, respectively
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4318187&req=5

Figure 1: Product ion scans of amlodipine and valsartan, respectively

Mentions: Mass spectrometric detection was carried out on an API 4000 triple quadrupole instrument equipped with an ESI source operated in the positive ion mode. The ESI source in positive ion mode was selected, as it increased the signal-to-noise ratio of the analytes, which helped in attaining the lower LOQ. During the optimization of the mass spectrometric parameters, strong and stable signals of analytes and internal standards were noted and the ion transitions m/z 409.2 → 238.1, 413.2 → 238.1 and 436.2 → 291.5, 445.3 → 300.4 were selected for the MRM of amlodipine, amlodipine-d4, valsartan, and valsartan-d9, respectively. The optimization of the source and compound parameters was done by syringe pump infusion of each analyte. The compound parameters were optimized as follows: declustering potential: 40 V, entrance potential: 10 V, collision cell exit potential: 7 V, and collision energy: 15 V for amlodipine and amlodipine-d4 and 16 V for valsartan and valsartan-d9. The source/gas parameters were optimized as follows: curtain gas: 25, collision gas: 5, ion source gas-1: 40, ion source gas-2: 60, ion spray voltage: 5500 V and temperature: 550°C. The product ion scans of amlodipine and valsartan are shown in Figure 1.


Development and Validation of a LC-MS/MS Method for the Simultaneous Estimation of Amlodipine and Valsartan in Human Plasma: Application to a Bioequivalence Study.

Jangala H, Vats P, Khuroo AH, Monif T - Sci Pharm (2014)

Product ion scans of amlodipine and valsartan, respectively
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4318187&req=5

Figure 1: Product ion scans of amlodipine and valsartan, respectively
Mentions: Mass spectrometric detection was carried out on an API 4000 triple quadrupole instrument equipped with an ESI source operated in the positive ion mode. The ESI source in positive ion mode was selected, as it increased the signal-to-noise ratio of the analytes, which helped in attaining the lower LOQ. During the optimization of the mass spectrometric parameters, strong and stable signals of analytes and internal standards were noted and the ion transitions m/z 409.2 → 238.1, 413.2 → 238.1 and 436.2 → 291.5, 445.3 → 300.4 were selected for the MRM of amlodipine, amlodipine-d4, valsartan, and valsartan-d9, respectively. The optimization of the source and compound parameters was done by syringe pump infusion of each analyte. The compound parameters were optimized as follows: declustering potential: 40 V, entrance potential: 10 V, collision cell exit potential: 7 V, and collision energy: 15 V for amlodipine and amlodipine-d4 and 16 V for valsartan and valsartan-d9. The source/gas parameters were optimized as follows: curtain gas: 25, collision gas: 5, ion source gas-1: 40, ion source gas-2: 60, ion spray voltage: 5500 V and temperature: 550°C. The product ion scans of amlodipine and valsartan are shown in Figure 1.

Bottom Line: The assay was found to be linear over the range of 0.302-20.725 ng/mL for amlodipine and 6.062-18060.792 ng/mL for valsartan.The method was successfully applied for the bioequivalence study of amlodipine and valsartan after oral administration of a fixed dose of the combination.Additionally, as required by the current regulatory bodies, incurred sample reanalysis was performed and found to be acceptable.

View Article: PubMed Central - PubMed

Affiliation: Clinical Pharmacology and Pharmacokinetics, Ranbaxy Research Laboratories, Gurgaon, India.

ABSTRACT
A reliable, simple, and robust liquid chromatography-tandem mass spectro-metric (LC-MS/MS) method has been developed and validated that employs solid-phase extraction for the simultaneous estimation of amlodipine and valsartan in human K3EDTA plasma using amlodipine-d4 and valsartan-d9 as internal standards. Chromatographic separation of amlodipine and valsartan was achieved on the Luna C18 (2)100A (150 × 4.6 mm, 5 μm) column using acetonitrile: 5 mM ammonium formate solution (80:20, v/v) as the mobile phase at a flow rate of 0.8 mL/min in isocratic mode. Quantification was achieved using an electrospray ion interface operating in positive mode, under multiple reaction monitoring (MRM) conditions. The assay was found to be linear over the range of 0.302-20.725 ng/mL for amlodipine and 6.062-18060.792 ng/mL for valsartan. The method has shown good reproducibility, as intra- and interday precisions were within 10% and accuracies were within 8% of nominal values for both analytes. The method was successfully applied for the bioequivalence study of amlodipine and valsartan after oral administration of a fixed dose of the combination. Additionally, as required by the current regulatory bodies, incurred sample reanalysis was performed and found to be acceptable.

No MeSH data available.


Related in: MedlinePlus