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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

Linear plot of the mean plasma concentration (ng/mL) versus time (hr) of amlodipine and valsartan, respectively (n=42); R: reference drug; T: test drug.
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Figure 3: Linear plot of the mean plasma concentration (ng/mL) versus time (hr) of amlodipine and valsartan, respectively (n=42); R: reference drug; T: test drug.

Mentions: Following analysis, the pharmacokinetic parameters were calculated by non-compartmental modeling of data using WinNonlin professional software (Version 5.0, Pharsight Corp., Mountain View, CA, USA). The peak plasma concentration (Cmax) and time to reach Cmax (Tmax) were read directly from the data. The total area under the plasma concentration-time curve from time zero to the last measurable concentration (AUC0→t) was calculated using the linear trapezoidal rule-extrapolation method. Figure 3 shows the linear plot of the mean plasma concentration (ng/mL) versus time (hr) for both analytes. The mean estimates of the pharmacokinetic parameters derived from the plasma concentration profiles are summarized in Table 5. Of the total reanalyzed samples, 205 samples for amlodipine and 178 samples for valsartan met the acceptance criteria, showing good reproducibility of the method.


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)

Linear plot of the mean plasma concentration (ng/mL) versus time (hr) of amlodipine and valsartan, respectively (n=42); R: reference drug; T: test drug.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Linear plot of the mean plasma concentration (ng/mL) versus time (hr) of amlodipine and valsartan, respectively (n=42); R: reference drug; T: test drug.
Mentions: Following analysis, the pharmacokinetic parameters were calculated by non-compartmental modeling of data using WinNonlin professional software (Version 5.0, Pharsight Corp., Mountain View, CA, USA). The peak plasma concentration (Cmax) and time to reach Cmax (Tmax) were read directly from the data. The total area under the plasma concentration-time curve from time zero to the last measurable concentration (AUC0→t) was calculated using the linear trapezoidal rule-extrapolation method. Figure 3 shows the linear plot of the mean plasma concentration (ng/mL) versus time (hr) for both analytes. The mean estimates of the pharmacokinetic parameters derived from the plasma concentration profiles are summarized in Table 5. Of the total reanalyzed samples, 205 samples for amlodipine and 178 samples for valsartan met the acceptance criteria, showing good reproducibility of the method.

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