Zinc is an essential trace element which is used in different pharmaceuticals and supplements [1]. In the form of zinc oxide, zinc is an integral part of skin care creams, pastes, and supplements [2,3]. In order to meet the stringent quality standards for pharmaceutical products, manufacturers and laboratories must employ validated methods as from the United States Pharmacopeia and National Formulary (USP-NF). In the course of their modernization activities, USP-NF also updated the zinc monograph and replaced the existing identification procedure with titration by ion chromatographic analyses. Ion chromatography (IC) qualified as a methodical approach for the zinc assay in General Chapter <591>, Zinc Determination [4]. The analysis involves separation of zinc using, e.g., L91 column material (Metrosep A Supp 10) followed by post-column reaction using 4-(2-pyridylazo)resorcinol (PAR) and subsequent detection at 530 nm. IC was validated according to USP procedures as a highly specific and accurate method to ensure product safety and quality.

All analyses are performed with a solution of ultrapure zinc oxide. No additional sample preparation is required unless stated in the individual USP monographs.

A sample stock solution is prepared by hydrolyzing 0.1868 g of ultrapure zinc oxide powder in 10 mL of 6 mol/L hydrochloric acid. This solution is made up to 100 mL in a volumetric flask with ultrapure water. The zinc concentration of this sample stock solution corresponds to 1500 μg/mL. To prepare the final sample solution, the sample stock solution is diluted 1:100 with 0.2% (w/v) HCl to obtain a final concentration of 15 μg/mL zinc.

The working standard solution is prepared from a certified 1000 μg/mL zinc standard.

Samples and standard solutions were injected directly into the IC (Figure 1) using an 889 IC Sample Center – cool. Zinc is separated from all other cations using L91 column material (Metrosep A Supp 10 - 250/4.0 and Metrosep A Supp 10 Guard/4.0) applying the MetPac™ PDCA (pyridine-2,6-dicarboxylic acid) eluent (concentrate dilution 1:5) followed by post-column reaction (PCR) with MetPac™ PAR and subsequent detection at a wavelength of 530 nm.

The calibration was performed using a single 15 μg/mL zinc standard injected six times. The sample was analyzed in duplicate.

The IC assay for zinc content was validated according to USP General Chapter <591>, Zinc Determination [4]. Ultrapure zinc oxide was analyzed for its zinc content. The accuracy of the zinc determination was calculated as 99% (Figure 2).

All acceptance criteria were fulfilled, e.g., asymmetry (tailing factor) for the zinc peak was <2, or the relative standard deviation of the standard solutions was <0.73% (n = 6, USP requirement no more than (NMT) 0.73) (Table 2).