Residual solvent analysis

Table 8.7 Summary of common gas chromatographic detectors used in residual solvent analysis [97]...

API-related organic impurities usually involves high performance liquid chromatography (HPLC)-based analytical methods, with relatively non-specific detection techniques such as Ultraviolet/Visible (UV/Vis) Spectrophotometry. Residual solvents analysis usually involves gas chromatography (GC)-based analytical methods, again with relatively non-specific detection techniques such as flame ionization (FID). GC-based methods are most appropriate for volatile analytes such as residual solvents, whereas HPLC-based methods are more appropriate for the relatively non-volatile and polar API-related analytes. 

Dwivedi, A.M. Residual solvent analysis in pharmaceuticals. Int. J. Pharm. Excip. 2003, 33-37. 

FIGURE I Example of a residual solvent analysis of a standard containing nine solvents at approximately 0.05 mg/mL. 

The preferred sample preparation method for residual solvent analysis of pharmaceuticals is direct injection of the dissolved sample (11,60). With this technique, the recovery is most reliable because there is no opportunity for recovery loss due to adsorption or entrapment. The other techniques involve a separation of the volatiles before the GC injection and there is a risk that the volatile will be trapped. Typical solvents for this analysis are water, dimethyl sulfoxide, benzyl alcohol, and dimethylformamide (11,12,61). The three latter solvents are chosen because they are higher-boiling than commonly used pharmaceutical solvents and thus elute after them and do not interfere with the analysis. Water offers the advantage that it contributes little interference with a flame ionization detector. 

Often interference effects from either solvents [74] or other components in sample matrices can cause significant problems especially with direct injection of such solutions. Headspace analysis has been shown to be of great value for residual solvent analysis in drug substance [75] and dmg product [76] because the drag itself is not introduced into the system. Similarly, residual solvent analysis in pharmaceuticals using thermal desorption [77] and solid phase microexttaction (SPME) [78] has been shown to be of benefit. For more con ilex matrices such as... 

So do not forget to test for it when performing residual solvents analysis on drugs. In basie medium the diketone-aleohol is obtained ... 

Since most PET radiopharmaceuticals are purified by chromatographic methods using organic solvent, a residual solvent analysis should be performed as a routine validation of a certain number of used batches. 

J. Washall and T. Wampler, A dedicated purge and trap/GC system for residual solvent analysis of pharmaceuticals. Am. Lab. 25 20C (1993). 

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