M1030-12-094

Selective and Sensitive Determination of Zinc in Various OTC
Formulations as per USP <591>
1122Hari Narayanan , Shibu Paul , Michael Chang , Leonel M Santos

12Metrohm USA Inc , USP

CONTACT INFORMATION: hari@metrohmusa.com

PURPOSE•RESULT••

Zinc compounds are used as an active pharmaceuticalingredient in various over-the-counter (OTC) zinccontaining formulations. Many of the zinc drug
substances and drug products used to be tested forassay by manual titration methods. USP hasembarked on a global initiative to modernizemonographs across all of its compendia to include
more selective and more sensitive methodologies.
USP has updated the General Chapter <591> ZINC
DETERMINATION to include a new ion
chromatography (IC) method for zinc products.
Individual zinc compounds in drug substances anddrug products monographs are updated by USP as
they become available. We tested the applicability of anew ion chromatography method for zinc oxide, zincoxide powder and zinc sulfate ophthalmic solution
using an alternative column, L91.

••Column equivalency was tested as per USP system suitability guidelines. Themethod was tested for zinc oxide, zinc oxide powder and zinc sulfate
ophthalmic solution. The system suitability and sample analysis results aresummarized in Table 1 below. As the individual monographs become available,
they are posted in the Pharmaceutical Forum (PF). Figure 4 shows themethods in the Pharmaceutical Forum (PF) and the others that are expectedsoon.

•••

Metrohm 940 Professional IC Vario
Detection: Vis 530 nm
Column Temperature: 30° C
Flow Rate: 1.2 mL/min
PCR Flow Rate: 0.6 mL/min
Injection Volume: 10 μL
Eluent : 4 mmol/L nitric acid - Isocratic separation
Column: Metrosep A Supp 10-250/4.0, packing L91

Fig 2: Zinc in zinc oxide sample as per USP <591>

T1030-07-0558
Fig 5: Ion Chromatography instrument used for OTC assay

METHOD
Ion Chromatography is suitable for metal cation
separation and detection. For zinc determination,
two methods are possible. Separation as cationicspecies and detection by non-suppressed
conductivity method, as shown in Figure 1, isvery simple and straightforward.
Alternatively, zinc is separated as anionic
dipicolinic acid complex using the L91 columnand converted to Zn-4‐(2‐pyridylazo) resorcinol(PAR) complex, after post column reaction, anddetected at 530 nm. The general instrumentation
schematic is outlined in Figure 3.
A precise and pulse-free post column reagent(PCR) is critical in this method. The ratio ofeluent to PCR volume is important to achieve aconsistent response. Precise and pulse-free postcolumn reagent delivery is achieved by patented
Metrohm Dosino technology. PCR addition andrinsing the flow path with water after the sample
queue can be automated with Dosino liquidhandling. The instrumentation used in this study
is shown in Figure 5.
Samples were prepared as per the individual
monograph guidelines.

CONCLUSION

Fig 3: Ion Chromatography with PCR- UV-VIS detection, flow path
Table 1: Result Summary

The new USP method for zinc as per <591> using Ion
Chromatography is highly selective and sensitive.
Selectivity is achieved by separation and further
improved with PCR reaction. Sensitivity and the wide
linear quantification limit make the new USP method
ideal for QA/QC. Automated PCR delivery makes theoverall method performance easy to validate.

8.000.6105EN

Fig 1: Zinc by Non-Suppressed Conductivity Detection; Column: L-76;
Eluent: 2.5 mmol/L Nitric acid + 0.5 mmol/L Oxalic acidFig.4: USP Monograph Modernization Progress