Edgar Alejandro de Leon-Diaz de Leon
◽
Antonio Gordillo-Moscoso
◽
Úrsula Medina
◽
Ángel Antonio Vertiz Hernández
◽
Rafael Almendra-Pegueros
◽
...
Background:
Losartan, one of the most frequently used drugs in Heart Failure (HF)
treatment, could be modified for its bioavailability (BA) by generic formulations and other factors.
Hence, the importance of therapeutic drug monitoring.
Objective:
Development and validation of a simplified analytical method using HPLC for simultaneous
quantification of losartan and E-3174 in human plasma samples. The method was tested for determining
the pharmacokinetics parameters of HF patients.
Methods:
Analytical conditions were optimized using a C18 column (4.6 X 50 mm, 3 μm. Thermo
Scientific) at 25ºC. Conditions of mobile phase: a phosphate buffer (0.01M), adjusted to pH 2.5 with
phosphoric acid (1M) and Acetonitrile (60:40 v/v). The flow rate was maintained at 1.2 mL/min, on a
running time of 5 min and a sample injection volume of 50 μL. Absorbance for measurement of
losartan and E-3174 was 200 nm. Pharmacokinetics profiles were determined with Phoenix Win-
Nonlin 8.1 software in a non-compartmental model.
Results:
Analytical method developed and validated in this work is precise and accurate for simultaneous
determination of losartan and E-3174 in human plasma samples in a range of 0.02 -10 μg/mL.
In HF subjects, lower Tmax and higher Cmax for losartan and E-3174 patent than generic formulation
were observed, which can be translated into less biological effect and more time to present it by
the generic drug.
Conclusion:
The pharmacokinetic profile is dependent on the type of formulation studied (generic/
patent) hence the importance of conducting evaluations in our patients to ensure that the expected
therapeutic effect is achieved with treatment administered.
Development and validation of a bioanalytical method for the simultaneous determination of heroin, its main metabolites, naloxone and naltrexone by LC–MS/MS in human plasma samples: Application to a clinical trial of oral administration of a heroin/naloxone formulation
