Analyte: chloride

The chloride ion, Cl^–, is the base of hydrochloric acid, HCl, which is a strong acid with a pKa of -6.3, and thus fully dissociated in all aqueous solutions regardless of pH. Chloride is singly charged and carries a hydration layer comprised of 2.0 associated water molecules. Some properties of the chloride ion are summarized in the table below.

Chloride analysis

Chloride is typically analysed by ion chromatography (IC) with suppressed conductivity detection along with the other common inorganic anions, and quite many different IC columns can accomplish the separation using either carbonate-bicarbonate eluents or hydroxide eluents. The full dissociation and rather high molar conductivity of the chloride ion results in high sensitivity when it is monitored by suppressed conductivity detection.

Many HILIC columns will also retain chloride, and this may thus be an alternative analysis technique, whereas reversed-phase (RP) and ion-exclusion chromatography (IEC, ICE) tend to not give sufficient retention.

Analysis of chloride is important in several industries, including food & beverage, pharmaceutical, energy & electronics, and environmental monitoring. As one of the seven common anions outlined in the WHO Guidelines for drinking-water quality, analysis of chloride is described in several standardized IC methods including US EPA 300.1, DIN/EN/ISO 10304-1, and ASTM D4327-17. Since chloride ion is the major component by weight in table salt (which is >97% sodium chloride, NaCl), its concentration is monitored in many processed food and beverages. Chloride is a frequent constituent of pharmaceutical formulations, both as counterion excipient in many tablets together with basic active ingredients, and as an active ingredient in several types of injection solutions, and its analysis is therefore described in several pharmacopoeia monographs. Trace levels of Cl^– ions are monitored in battery electrolyte raw materials and circuit board manufacturing since its presence may disturb various electric processes. Because chloride is a corrosive agent, it is important to control its level in several industrial settings including heat exchangers, and also in building materials such as concrete.

Table of some chloride ion properties at 25 °C

Ion	Molecular weight, M	Molar conductivity, λ₀	Diffusion coefficient, D	Ionic radius, r	Hydration shell, Δr
	(g/mol)	(S·cm²/mol)	(mm²/ms)	(pm)	(pm)
Chloride, Cl^–	35.454	76	2.03	180	43
M, was retrieved from Chemical Aid Molecular Mass Calculator. Values for λ₀ & D, are from CRC Handbook of Chemistry and Physics, 75th Ed., D.R. Lide (Ed.), CRC Press Inc. (1994), Boca Raton, pp 5-90 to 5-92. Data for r & Δr, plus the number of water molecules, n, mentioned in the text, are from Y. Marcus, J. Chem. Soc. Faraday Trans., 87 (1991) 2995-2999. The pKa values mentioned in the text are from Organic Chemistry Data pKa compilation.

Learn more

To learn more, browse the application examples below or contact Diduco to discuss your specific analysis.

Applications

ion chromatography

Published case study of analytical quality by design method development and validation

Diduco has published a scientific peer-reviewed case study on how modern analytical method development can be performed in the pharmaceutical industry. The work was performed according to analytical quality by design (AQbD) principles to establish the design space and robust setpoint of the ion chromatography assay, and then validated according to the guidelines established by the International Council for Harmonization (ICH).

ion chromatography

Preserving eluent quality with dedicated storage protected from ambient carbon dioxide

To ensure that liquid chromatography analysis methods meet regulatory demands of retention repeatability as dictated by pharmacopoeia and the ICH guidelines, it is important to protect weakly buffered eluents from ambient carbon dioxide. The formation of carbonate species will otherwise change the pH and strength of the eluent, thus shifting retention.

ion chromatography

Screening of contaminants and forced degradation products in lithium ion battery electrolyte

Electrolytes in rechargeable batteries for cars, mobile phones, and other portable electric devices typically contain negatively charged counterions that together with lithium and a non-aqueous solvent form an ionic liquid. The bis(fluorosulfonyl)imide anion is a rather new ionic liquid constituent which thus need new quality control procedures.

ion chromatography

Comparing suppressed and non-suppressed ion chromatography

Suppressed ion chromatography with conductivity detection is a powerful and sensitive technique to analyse charged ionic species, especially anions of strong acids. The chemically regenerated membrane suppressor Xenoic® XAMS can enable analysis of such anions down to levels of a few microgram per litre (part per billion, ppb).

ion chromatography

Quantification of common anions in bottled drinking water according to EPA method 300.1A

Official procedure for quality control of drinking water according to the United States Environmental Protection Agency. This procedure allows quantification of the seven common inorganic anions fluoride, chloride, nitrite, bromide, nitrate, phosphate and sulfate in the ranges recommended by WHO and national authorities.

ion chromatography

Generic method for isocratic separation of fifteen common pharmaceutical counterions

Many medicines and dietary supplements are bases that carry a positive charge, and consequently these small molecules are accompanied by negatively charged counterions. Such anionic excipients may influence the properties of the pharmaceutical formulation and can also influence the effect of the active ingredient since different ion pairs can have different dissolution rates or abilities to penetrate cell walls.

ion chromatography

Analysis of dietary supplement capsules with glucosamine using a generic method for counterions

Oral glucosamine is a dietary supplement that is marketed to support the structure and function of joints and claimed to provide pain relief for people with arthritis and osteoarthritis, although there is no clear evidence that its benefit is significantly above placebo.

ion chromatography

Alternative method for determination of voriconazole impurity E

Voriconazole is an antifungal medication that is included on the WHO Model list of Essential Medicines. During synthesis of the active ingredient a resolving agent for chiral amines is often used, and it is thus necessary that the quality control prove that this substance is not present at harmful levels in the final product.

ion chromatography

Hydroxide gradient elution of organic acids and inorganic anions

Gradient elution is a powerful tool when aiming to separate many compounds having a wide range of different chemical characteristics. Hydroxide gradients are the most common in ion chromatography since they can be converted into pure water with nearly zero conductivity.

ion chromatography

Generic method for isocratic separation of ten common pharmaceutical counterions

ion chromatography

Quantification of common anions in drinking water according to EPA method 300.0A

Older version of the official procedure for quality control of drinking water according to the United States Environmental Protection Agency.

ion chromatography