Improve Pass Rates for Residual Solvents by USP Using the new Rxi®-624Sil MS GC Column

By Rick Lake, Pharmaceutical Market Development Manager and Amanda Rigdon, Innovations Chemist

• Greatest resolution of acetonitrile and dichloromethane of any G43.
• Symmetric peak shape for basic compounds like pyridine.
• Exceptional column-to-column reproducibility.

It has been over a year since the revised and more comprehensive USP Residual Solvents became effective. Since then, many labs have experienced difficulty implementing this more expansive general chapter. Two of the most problematic areas are test article solubility and variability in system suitability pass rates. The majority of problems in both these areas generally relate to the sensitivity and selectivity needed to meet the system suitability requirements in Procedure A. Finding an instrument setup that achieves acceptable carbon tetrachloride sensitivity in the Class 1 standard solution, while also maintaining an acceptable resolution between acetonitrile and dichloromethane in the Class 2 Mixture A standard solution, can prove difficult. Since increasing system suitability pass rates directly increases lab productivity, Restek has developed a new G43 capillary column that better meets the requirements of Procedure A. In this article, we will illustrate some column properties that can improve data quality for Procedure A according to USP.

Greater Resolution Improves Pass Rates

The Class 2 Mixture A solution contains the most difficult selectivity requirement of the method: the resolution between acetonitrile and dichloromethane (methylene chloride) must be greater than 1. This is often difficult to achieve on conventional G43 columns, which only give marginal selectivity for this pair. Poor selectivity can result in lower overall pass rates, and, thus, decreased sample throughput as this resolution requirement is not consistently met. In contrast, the Rxi®-624Sil MS column incorporates a distinctive bonding chemistry that results in resolution values consistently greater than 4 (Figure 1). The greater resolution routinely achieved on the Rxi®-624Sil MS column results in more consistent system suitability pass rates, and thus greater lab productivity.

Figure 1: Rxi®-624Sil MS columns reliably resolve Class 2 Mix A compounds, thus increasing system suitability pass rates.

methanol acetonitrile dichloromethane trans-1,2-dichloroethene cis-1,2-dichloroethene tetrahydrofuran cyclohexane methylcyclohexane 1,4-dioxane toluene chlorobenzene ethyl benzene m-xylene / p-xylene o-xylene Column: Rxi®-624Sil MS, 30m, 0.32mm ID, 1.8µm (cat.# 13870) Sample: 20µL Residual Solvents Class 2 Mix A Stock Solution (cat.# 36271) in 6mL water in a 20mL headspace vial (Concentration not consistent with USP methodology.) Inj.: 1.0mL manual headspace injection, split (3:1), 1mm split liner (cat.# 20972) Inj. temp.: 140°C Carrier gas: helium, constant flow Flow rate: 2.2mL/min. Oven temp.: 40°C (hold 20 min.) to 240°C @ 10°C/min. (hold 20 min.) Det.: FID @ 250°C Hydrogen: 40mL/min. Air: 450mL/min. Makeup: 45mL/min. Instrument: Agilent 6890 GC_PH01116

Higher Inertness Gives Increased Sensitivity

Rxi®-624Sil MS columns are manufactured using proprietary Rxi® technology, which produces extremely inert columns. Column inertness, in combination with selectivity, contributes to resolution and can greatly affect overall data quality. For example, carbon tetrachloride in the Class 1 system suitability solution presents the most difficult sensitivity requirement in the method. On the Rxi®-624Sil MS column, carbon tetrachloride is easily resolved from 1,1,1-trichloroethane, allowing consistent integration; in addition, the resolution of benzene and 1,2-dichloroethane is also complete (Figure 2). The baseline resolution of these analytes is advantageous as it allows consistent and accurate integration, which reduces the chance of failing sensitivity requirements for carbon tetrachloride. Complete resolution of these analytes is often not achieved on competitive columns, making the Rxi®-624Sil MS column particularly beneficial for testing programs using USP .

Figure 2: The Rxi®-624Sil MS column provides complete resolution of the USP Class 1 solution components—a result not often achieved on other G43 columns.

1,1-dichloroethene 1,1,1-trichloroethane carbon tetrachloride benzene 1,2-dichloroethane Column: Rxi®-624Sil MS, 30m, 0.32mm ID, 1.8µm (cat.# 13870) Sample: 2µL Residual Solvents Class 1 Stock Solution (cat.# 36279) in 6mL water in a 20mL headspace vial. (Concentration not consistent with USP methodology.) Inj.: 1.0mL manual headspace injection, split (3:1), 1mm split liner (cat.# 20972) Inj. temp.: 140°C Carrier gas: helium, constant flow Flow rate: 2.2mL/min. Oven temp.: 40°C (hold 20 min.) to 240°C @ 10°C/min. (hold 20 min.) Det.: FID @ 250°C Hydrogen: 40mL/min. Air: 450mL/min. Makeup: 45mL/min. Instrument: Agilent 6890 GC_PH01115

Another distinct advantage can be seen when analyzing the Class 2 Mix B solution. The peak shape for pyridine (a basic compound) often tails significantly on conventional G43 columns. The inertness of the Rxi®-624Sil MS column produces very symmetric peak shapes for basic compounds, which results in a higher response and more accurate integration (Figure 3). The deactivation of the Rxi®-624Sil MS column results in a highly inert column that is well-suited for both acidic and basic compounds and is fully compatible with all Class 1 and 2 residual solvents.

Figure 3: Highly inert Rxi®-624Sil MS columns ensure excellent peak shape for pyridine in the Class 2 Mix B.

hexane nitromethane chloroform 1,2-dimethoxyethane trichloroethylene pyridine 2-hexanone DMSO tetralin Column: Rxi®-624Sil MS, 30m, 0.32mm ID, 1.8µm (cat.# 13870) Sample: 83µL Residual Solvents Class 2 Mix B Stock Solution (cat.# 36280) in 6mL water in a 20mL headspace vial. (Concentration not consistent with USP methodology.) Inj.: 1.0mL manual headspace injection, split (3:1), 1mm split liner (cat.# 20972) Inj. temp.: 140°C Carrier gas: helium, constant flow Flow rate: 2.2mL/min. Oven temp.: 40°C (hold 20 min.) to 240°C @ 10°C/min. (hold 20 min.) Det.: FID @ 250°C Hydrogen: 40mL/min. Air: 450mL/min. Makeup: 45mL/min. Instrument: Agilent 6890 GC_PH01117

Conclusion

Not all G43 columns are equivalent for residual solvent testing, and the new Rxi®-624Sil MS column offers best-in-class performance advantages for all aspects of USP system suitability testing. These columns reliably produce improved resolution and sensitivity, increasing system suitability pass rates and ensuring more productive laboratory time.

For more information on residual solvent testing, visit www.restek.com/usp467