Filling Gaps on Stability Data: Development, Validation and Application of a Multianalyte UHPLC-DAD Method to Determine the Stability of Commonly Administered Drugs in Different Carrier Solutions Used in Palliative Care

Christian Steuer,Ursina Müller,Peter Wiedemeier,Fiona Haller

doi:10.3390/analytica1010005

Abstract

In palliative care, continuous subcutaneous infusion (CSCI) is common practice for drug administration when oral application of drugs is not feasible or not reliable anymore. However, use of CSCI is limited to chemical stability of drugs and their combination in carrier solution. To determine the stability of different mixtures of commonly used drugs in palliative care, a multi-analyte UHPLC-DAD method controlled by an internal standard was successfully developed. The method was validated in terms of specificity, accuracy, precision, and linearity across the calibration range. Seven analytes could be separated within 10 min by C18-reversed phase chromatography. The method was successfully applied to close gaps in stability data and complete missing data for decision makers in health care units. Our results indicated the stability of binary mixtures and one ternary mixture in 0.9% saline and 5% glucose as carrier solutions. The obtained data will support pharmacists in palliative care for the preparation of parenteral drug solutions in the future.

Highlights

In palliative and critical care, drugs are often administered parenterally, since many patients cannot take drugs orally due to persistent nausea and/or vomiting, dysphagia, bowel obstruction or malabsorption, significant tablet burden or reduced level of consciousness such as in the last days of life
Analytical reference standards of Dex, metoclopramide hydrochloride (Met), haloperidol lactate (Hal), Sco, morphine hydrochloride (Mor), midazolam hydrochloride (Mid), levomepromazine hydrochloride (Lev) and formic acid were obtained from Sigma Aldrich (Buchs, Switzerland)
No data were available on the combination of Lev with either Hal, Sco or Met

Summary

Introduction

In palliative and critical care, drugs are often administered parenterally, since many patients cannot take drugs orally due to persistent nausea and/or vomiting, dysphagia, bowel obstruction or malabsorption, significant tablet burden or reduced level of consciousness such as in the last days of life. In these situations, continuous subcutaneous infusion (CSCI) has become common practice [1]. For the continuous application of drugs, syringe pumps, known as syringe drivers, are often used [4] They allow for the administration of mixtures of drugs. CSCI applications further minimize pricking events which improves the compliance among patients and their relatives [5]

Methods

Results

Discussion

Conclusion