T1530-12-0918

Potassium Assay in OTC Drug Products by Ion Chromatography
1233
Hari Narayanan , Uvaraj Mani , Michael Chang , Leonel M Santos123Metrohm USA Inc , Metrohm India Limited , USP

CONTACT INFORMATION: hari@metrohmusa.com

PURPOSE•RESULT

••

Pharmaceutical laboratories rely heavily onmonographs from the United States Pharmacopeia
and National Formulary (USP–NF) to build theiranalytical methods. USP has embarked on a global
initiative to modernize monographs with selectiveand sensitive methodologies to replace outdated
wet chemistry methods. In the current monographfor POTASSIUM BICARBONATE ANDPOTASSIUM CHLORIDE EFFERVESCENTTABLET FOR ORAL SUSPENSION, identificationis performed by a wet chemistry method, andassay is determined by Atomic Absorption
Spectroscopy (AAS). We propose a selective andsensitive ion chromatography (IC) method for thepotassium assay drug product, which can also beused for the identification application.

••Optimized chromatographic conditions offered the best selectivity for potassium. Specificity
was checked with diluent, resolution solution, standard solution, and sample solution to ensure
no interference or co-elution with the potassium peak (Figure. 1). The linearity of potassium
was investigated over the concentration range from 3. 75 mg/L to 22. 5 mg/L of potassium
covering 25% to 150% of the expected potassium concentration. An overlay of thesechromatograms is shown in Figure 2. The correlation coefficient was found to be 0. 9999 andthe calculated Y-intercept bias was 0. 5% of the 100% linearity level response (figure. 3).
Method validation elements of specificity, linearity, system suitability, solution stability, accuracy
and precision, and intermediate precision and accuracy were investigated. Validation results
met the acceptance criteria and are summarized in Table1. The data demonstrated that theassay procedure can be used for the ID of potassium in potassium bicarbonate and potassium
chloride effervescent tablet for oral suspension.

••••

Metrohm 940 Professional IC Vario
Detection: Direct Conductivity Detection
Column Temperature: 30° C
Flow Rate: 0.9 mL/min
Injection Volume: 20 μL
Run Time: 20.0 min
Eluent : 4 mmol/L nitric acid - Isocratic separation
Metrosep C 6 - 150/4.0, 4mm × 150 mm, packing L76
Metrosep C 6 Guard/4.0

Fig 1: Specificity: Resolution solution

Fig 3: Ion Chromatography instrument used for OTC AssayMETHOD
Ion chromatography (IC) is suitable for separationand quantification of mono- and divalent cations
and many aliphatic amines in pharmaceuticalmatrices. Typically, a non-suppressed conductivity
detection that resembles a standard HPLC flow
path is the preferred method for cation species
analysis. Key advantages of non-suppressed
conductivity detection are:CONCLUSION

Fig 2: Linearity: Chromatograms overlay••••Linear calibration curve over a wide range
Organic solvents as part of eluent composition
No metal hydroxide formation
EconomicalIn this case, a cation exchange column, Metrosep
C6-150/4. 0mm with L76 packing and 4 mmol/L
nitric acid as the eluent and a flow rate of 0. 9mL/min, was used. We transferred and dissolved
approximately 50 g of finely powdered Potassium
25 mEq tablets to a 2000 mL volumetric flask(equivalent to 10 tablets' weight), added 200 mL ofDI water, swirled until effervescence ceased,
diluted to volume with DI water, and mixed well.
The method is validated according to USPGeneral Chapter <1225> VALIDATION OFCOMPENDIAL METHODS

We successfully developed and validated a single IC
procedure for potassium assay and identification inpotassium bicarbonate and potassium chloride for
effervescent oral suspension. The optimized
chromatographic conditions can be used for othercationic impurities, such as magnesium, calcium,sodium, and ammonium in potassium bicarbonate andpotassium chloride for effervescent oral suspension. Asingle chromatographic method for assay andidentification simplifies the overall QA/QC workflow.

8.000.6106EN

Table 1: Validation SummaryFig 3: Linearity for Potassium