Method for the Determination of Pd-Catalyst Residues in Active Pharmaceutical Ingredients by Means of High-Energy Polarized-Beam Energy Dispersive X-Ray Fluorescence

Abstract

In medicinal chemistry, Pd is perhaps the most-widely utilized precious metal, as catalyst in reactions which represent key transformations toward the synthesis of new active pharmaceutical ingredients (APIs). The disadvantage of this metal-catalyzed chemistry is that expensive and toxic metal residues are invariably left bound to the desired product. Thus, stringent regulatory guidelines exist for the amount of residual Pd that a drug candidate is allowed to contain. In this work, a rapid and simple method for the determination of Pd in API samples by high-energy polarized-beam energy dispersive X-ray fluorescence spectrometry has been developed and validated according to the specification limits of current legislation (10 mg kg(-1) Pd) and the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH guidelines). Sample and calibration standards preparation includes a first step of homogenization and then, in a second step, the pressing of the powdered material into pellets without any chemical treatment. The use of several synthetic calibration standards made of cellulose to simulate the API matrix appears to be an effective means to obtain reliable calibration curves with a good spread of data points over the working range. With the use of the best measuring conditions, the limit of detection (0.11 mg kg(-1) Pd) as well as the limit of quantitation (0.37 mg kg(-1) Pd) achieved meet rigorous requirements. The repeatability of the XRF measurement appeared to be less than 2%, while the precision of the whole method was around 7%. Trueness was evaluated by analyzing spiked API samples at the level of the specification limit and calculating the recovery factor, which was better than 95%. To study the applicability of the developed methodology for the intended purpose, three batches of the studied API were analyzed for their Pd content, and the attained results were comparable to those obtained by the daily routine method (acid digestion plus atomic spectroscopy) used in most pharmaceutical laboratories.

Polarization Dependence of Low-Frequency Vibrations from Multiple Faces in an Organic Single Crystal

“…Light polarization determination and manipulation are crucial for many optical applications. Light polarization is essential for many metrology applications such as stress analysis [21], pharmaceutical ingredient analysis [22], and biological microscopy [23], as dependence on light polarization indicates the polarizability of the measured chemical interactions. Different polarizations of light may enrich color diversity in devices by ranging degrees of absorption in different materials, an essential property for LCD screens [24], 3D movies [25], and glare-reducing sunglasses [26].…”

X‐ray Fluorescence Investigation of Ordered Intermetallic Phases as Electrocatalysts towards the Oxidation of Small Organic Molecules

“…X-ray fluorescence (XRF) is a widely used analytical technique employed in different fields, [13][14][15] such as environmental studies, [16] medicine, [17] polymers, [18] biology, [19] botany, [20] archeology, [21] pharmacology, [22] and planetary studies. [23] Attractive features of the XRF technique include the fact that it is nondestructive, has high elemental selectivity, simplicity of quantification, and low detection limits.…”

An efficient continuous flow approach to furnish furan-based biaryls

“…As context the European Agency for the Evaluation of Medicines states that for oral administration the permitted daily exposure of class A1 metals such as palladium should not exceed 10 mg kg -1 and thus the Pd content of 7 is within this guideline. 39,40 While the optimised protocol efficiently furnished 7, the practicality of this continuous flow approach could only be judged by amenability to aryl bromide variations. Thus, the coupling of a small library of aryl bromides, sulfonamide based aryl bromides, and an amide based aryl bromide was investigated.…”