Simultaneous Quantification of Ramipril and Ramiprilat in Drug Formulations: A Clinical LC-MS/MS Study

Determination of Ramipril and Ramiprilat

Abstract

Ramipril is a drug controlling hypertension. Two drugs were studied in 36 healthy adults. The drugs are the test (Atb^®) and the reference (Tritace^®). This concept is crucial in the pharmaceutical industry during the development process. The maximum concentration (C_max) of Ramipril and its metabolite (Ramiprilat) were determined throughout drug administration in healthy subjects. All analysis was performed using LC-MS/MS. The method was validated over a range of 0.200 – 25.000 ng/mL in which linearity (R²) was 0.9983, accuracy was 99.9%, precision (CV) was less than 20%, and the Lower Limit of Quantitation was 0.200 ng/mL. Stability and other parameters were discussed. The time needed to reach this concentration (T_max) and the time-drug concentration area under the curve (AUC) were most agreed upon. The two drugs were proven to be interchangeable. Both have similar pharmacokinetics and bioequivalence profiles. Consequently, the drugs are bioequivalent and considered alternatives to one another pharmaceutically. For example, 90% confidence intervals (C.I.) for the in-tra-individual ratios (test/reference) for pharmacokinetic parameters were C_max, and AUC_0-t for total exposure C.I. Log – transformed Values were 80-125 %.