A new LC-MS/MS bioanalytical method for perindopril and perindoprilat in human plasma and milk

Abstract

A first of its kind, simple, rapid, and sensitive liquid chromatography mass spectrometry (LC-MS/MS) method was developed and validated for quantification of perindopril and perindoprilat in both human plasma and breast milk. The analytes and internal standards (phenazone and acetyl salicylic acid) were extracted from biological matrices by protein precipitation. A Phenomenex® C-18 column was used to provide an appropriate chromatographic separation of the analytes, followed by detection with tandem mass spectrometry. Gradient chromatographic and mass spectrometric detection conditions with mobile phases (A: 5% methanol + 0.1% formic acid in water v/v, and B: 95% methanol + 0.1% formic acid in water v/v) were developed to achieve a LOQ of 0.5 ng/mL in both human plasma and milk. The method was suitable of evaluating clinical samples. The mass transition was followed as m/z 369.10/172.00 for perindopril, m/z 339.00/168.10 for perindoprilat, m/z 188.90/55.95 for phenazone, and m/z 179.04/137.02 for acetyl salicylic acid. The developed method was optimized and validated with a linear range of 0.1-200 ng/mL (r = better than 0.99 for both perindopril and perindoprilat). The precision and accuracy values were within 15% CV. The overall recovery of the analytes was 80-110%. The method has good specificity and repeatability. Stability studies were conducted in both human plasma and bovine milk for up to 3 months, at the storage conditions of 25, 4, and -80 °C.

Transfer of rosuvastatin into breast milk: liquid chromatography–mass spectrometry methodology and clinical recommendations

“…The spiked samples were mixed thoroughly by vortex mixing for approximately 1 minute. Our previously developed protein precipitation and ultracentrifugation methods 3 , 9 , 10 were used for the separation of rosuvastatin from biological samples. Drug-free human plasma and milk samples were used as negative controls.…”

<p>Perindopril in Breast Milk and Determination of Breastfed Infant Exposure: A Prospective Observational Study</p>

“…Breast milk and plasma concentrations of perindopril and perindoprilat were analysed using our previously validated Liquid Chromatography tandem-Mass Spectrometry (LC-MS/MS) method. 14…”

Postpartum Cardiomyopathy and Considerations for Breastfeeding

“…For other ACE inhibitors, where evidence is available, only very small amounts of the parent drug and its active metabolite have been found in breast milk. 35,36,37,38,39,40 Enalapril is often the preferred option since it has the most published data supporting its use. One study calculated the level of infant exposure to enalapril as 0.16 % of the maternal weight-adjusted dose.…”