Determination of Elemental Impurities in Sorbitol as Pharmaceutical Excipient Application Note · PlasmaQuant 9100 Elite

Introduction

As all polyols, sorbitol and sorbitol syrup are sugar alcohols or hydrogenated carbohydrates. They are also known as sugar replacers, bulk sweeteners or sugarfree sweeteners. Sorbitol is widely used as a pharmaceutical excipient in direct compression applications to produce tablets, where it provides bulk to the drug products. Especially in modern formulations, like consumer-friendly lozenges or chewable tablets, sorbitol has gained popularity due to its sweet taste and toothfriendliness. But also in conventional tablets the usage of polyols is increasing.

Pharmaceutical excipients are substances other than the active pharmaceutical ingredient (API) that are intentionally included in an approved drug delivery system or a finished drug product. Therefore, they need to be considered as part of the risk assessment for elemental impurities in final pharmaceutical products. The limits and the type of impurities for each excipient are usually specified in monographs by the issuing Pharmacopoeia. For instance, the European Pharmacopoeia defines the limits for nickel (<1.0 ppm) and lead (<0.5 ppm) in sorbitol products that are used as excipients for the manufacturing of pharmaceuticals.

Since sorbitol is predominantly used in the manufacturing process of tablets for oral administration, class 1 and class 2A trace elemental impurities defined in USP <232> are often analyzed alongside nickel and lead. Due to the release ofUSP chapters <232> and <233> as well as the ICH Q3D guidelines, ICP-OES and ICP-MS have found their way as a routine instrumentation into the QC labs of the pharmaceutical industry.

Sample transportation into an ICP system requires the dilution of viscous samples such as sorbitol in order to ensure reliable aerosol formation in the spray chamber/nebulizer system. At the same time, sample dilution is desired to be kept at a minimum level in order to not compromise the achievable limits of quantification of the employed method. Hence, aspirating high matrix samples into an ICP requires a robust plasma and a vertically oriented torch system. In this regard, the PlasmaQuant 9100 Elite ICP-OES offers a high-frequency generator in combination with the unique V-Shuttle torch, which can handle high matrix loadings up to saturated salt solutions. This enables the analyst to run small dilution factors. In combination with the high sensitivity of the instrument, low method-specific limits of quantification can be achieved, which is crucial when analyzing trace elements defined in USP regulations. Commonly occurring interferences in ICP-OES are addressed by the high-resolution optical system of the PlasmaQuant 9100 Elite, which allows for an interference-free analysis of trace elements in typical pharmaceutical matrices.