You have been redirected to your local version of the requested page

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.

Figure 1. Instrumental setup including a 930 Compact IC Flex with a 947 Professional UV/VIS Detector Vario, a 800 Dosino for PCR delivery and mixing, and an 889 IC Sample Center – cool. Cooling can prolong sample stability.

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

Table 1. Requirements for IC method as per USP General Chapter <591>.

Column with L91 packing Metrosep A Supp 10 - 250/4.0
Eluent MetPac™ PDCA concentrate (dilution 1:5)
Flow rate 1.2 mL/min
Temperature 30 °C
Injection volume 10 μL
PCR reagent PAR (0.12 g MetPac™ PAR reagent in 1000 mL MetPac™ PAR diluent)
PCR flow rate 0.6 mL/min
Detection Vis: 530 nm after PCR

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).

Table 2. Required acceptance criteria according to General Chapter <591>. 

Parameter Actual USP requirement Status
% RSD 0.582 NMT 0.73 Pass
Tailing factor 1.465 NMT 2.0 Pass
Result standard 98.9% +/- 2%* Pass
Results sample 99.2% +/- 2%* Pass
* of the certified value
Figure 2. Chromatogram of zinc in a zinc oxide sample containing 14.865 μg/mL Zn (99.1% recovery of the nominal concentration).

Ion chromatography qualifies for the determination of zinc as per USP General Chapter <591>. Using the column material L91, zinc can be reliably determined in pharmaceuticals and other samples using IC with post-column reaction and UV detection.

The high degree of automation possibilities for IC systems from Metrohm (e.g., autosampler, Metrohm intelligent Partial Loop injection Technique, Inline Dilution, etc.) and the traceability of all steps during analysis make it a user-friendly, efficient, and valuable analytical technique for pharmaceutical quality control processes.

  1. Royal Society of Chemistry. Zinc. The Royal Society of Chemistry’s interactive periodic table.
  2. Juch, R. D.; Rufli, T.; Surber, C. Pastes: What Do They Contain? How Do They Work? Dermatology 1994, 189 (4), 373–377.
  3. Maier, T.; Korting, H. C. Sunscreens - Which and What For? Skin Pharmacol Physiol 2005, 18 (6), 253–262.
  4. U. S. Pharmacopeia/National Formulary. <591> Zinc Determination. In General Chapter; USP/NF, Rockville, MD, USA.

Metrohm USA

9250 Camden Field Pkwy
33578 Riverview, FL