Charged aerosol detection in early and late-stage pharmaceutical development: selection of regressionmodels at optimum power function value.

In recent years, the use of quantitative liquid chromatography (LC) coupled charged aerosol detection (CAD) for poor UV absorbing analytes in multicomponent mixtures has grown exponentially across academic and industrial sectors. The ballpark of previous LC-CAD reports is focused on practical applications, as well as optimization of critical parameters such as: response dependencies on temperature, nebulization process, analyte volatility, and mobile-phase composition. However, straightforward approaches to deal with the characteristic nonlinear response of CAD still scarce.

Revealing the inner workings of the power function algorithm in Charged Aerosol Detection: A simple and effective approach to optimizing power function value for quantitative analysis.

In recent years, charged aerosol detection (CAD) has become a valuable tool for fast and efficient quantitative chromatographic analysis of drug substances with weak UV absorption. In analytical method development using CAD, the power function settings available in the instrument software are key for linearization of the signal response with respect to analyte concentration. However, the relatively poor understanding of the power function algorithm has limited a more widespread use of CAD for quantitative assays, especially in the late stage of method validation and GMP laboratories.

Kinetics and Degradation Mechanism of Adrenaline Derivative CpQ in Diluted Aqueous Solutions.

The degradation kinetics of an adrenaline (epinephrine) derivative, CpQ, was studied in solution in the pH range of 1-12 at 40-80 °C by high-performance liquid chromatography and ultraviolet-visible spectroscopy. The pH-rate profile exhibits a bell-shaped curve with two sigmoidal regions in the specific acid-catalyzed and specific base-catalyzed regions. The pH range of maximum stability was 2.

A four parameter optimization and troubleshooting of a RPLC - charged aerosol detection stability indicating method for determination of S-lysophosphatidylcholines in a phospholipid formulation.

A four parameter optimization of a stability indicating method for non-chromophoric degradation products of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), 1-stearoyl-sn-glycero-3-phosphocholine and 2-stearoyl-sn-glycero-3-phosphocholine was achieved using a reverse phase liquid chromatography-charged aerosol detection (RPLC-CAD) technique. Using the hydrophobic subtraction model of selectivity, a core-shell, polar embedded RPLC column was selected followed by gradient-temperature optimization, resulting in ideal relative peak placements for a robust, stability indicating separation. The CAD instrument parameters, power function value (PFV) and evaporator temperature were optimized for lysophosphatidylcholines to give UV absorbance detector-like linearity performance within a defined concentration range.

Cleaning verification: A five parameter study of a Total Organic Carbon method development and validation for the cleaning assessment of residual detergents in manufacturing equipment.

A Total Organic Carbon (TOC) based analytical method to quantitate trace residues of clean-in-place (CIP) detergents CIP100 and CIP200 on the surfaces of pharmaceutical manufacturing equipment was developed and validated. Five factors affecting the development and validation of the method were identified: diluent composition, diluent volume, extraction method, location for TOC sample preparation, and oxidant flow rate. Key experimental parameters were optimized to minimize contamination and to improve the sensitivity, recovery, and reliability of the method.

Failure of Cleaning Verification in Pharmaceutical Industry Due to Uncleanliness of Stainless Steel Surface.

The aim of this work is to identify the parameters that affect the recovery of pharmaceutical residues from the surface of stainless steel coupons. A series of factors were assessed, including drug product spike levels, spiking procedure, drug-excipient ratios, analyst-to-analyst variability, intraday variability, and cleaning procedure of the coupons. The lack of a well-defined procedure that consistently cleaned the coupon surface was identified as the major contributor to low and variable recoveries.

A simplified guide for charged aerosol detection of non-chromophoric compounds-Analytical method development and validation for the HPLC assay of aerosol particle size distribution for amikacin.

Amikacin, an aminoglycoside antibiotic lacking a UV chromophore, was developed into a drug product for delivery by inhalation. A robust method for amikacin assay analysis and aerosol particle size distribution (aPSD) determination, with comparable performance to the conventional UV detector was developed using a charged aerosol detector (CAD). The CAD approach involved more parameters for optimization than UV detection due to its sensitivity to trace impurities, non-linear response and narrow dynamic range of signal versus concentration.

Cleaning verification: Exploring the effect of the cleanliness of stainless steel surface on sample recovery.

The parameters affecting the recovery of pharmaceutical residues from the surface of stainless steel coupons for quantitative cleaning verification method development have been studied, including active pharmaceutical ingredient (API) level, spiking procedure, API/excipient ratio, analyst-to-analyst variability, inter-day variability, and cleaning procedure of the coupons. The lack of a well-defined procedure that consistently cleaned coupon surface was identified as the major contributor to low and variable recoveries. Assessment of acid, base, and oxidant washes, as well as the order of treatment, showed that a base-water-acid-water-oxidizer-water wash procedure resulted in consistent, accurate spiked recovery (>90%) and reproducible results (S≤4%).