Volumetric analysis of drugs

Solid-state samples can be prepared by accurately weighing the drug substance into a container that can be stored under the appropriate condition. Suitable containers include volumetric flasks, scintillation vials, etc. The amount of drug substance used is usually dictated by the availability of material, accuracy of balances, and the final concentration desired for analysis. Typical amounts used for solid-state samples would be between 2 and... 

Subert, J. Drug analysis. VI. Studies of conditions for dia-zotizing titrations of drugs with potentiometric indication and standardization of a volumetric sodium nitrite solution. Farm. Obz. 1981, 50, 273-278. 

Identification testing of indapamide drug substance can be accomplished by UV absorbance spectrophotometric analysis. A 35-40 mg sample of indapamide is weighed into a 50-mL volumetric flask. The drug substance is dissolved and brought to volume with methanol. The solution is then diluted 1 to 10 with methanol and a portion placed in a 1-cm cell. The spectrum is recorded from 260 to 325 nm using methanol as a blank. There should be maxima at about 286 nm and 278 nm and minima at about 282 nm and 271 nm. The resultant spectrum also exhibits characteristics at the same wavelengths as a similarly prepared and concomitantly measured indapamide reference standard. 

CP-944,629 is a substituted l,2,4-triazolo[4,3-a]pyridine. This compound was designed as a selective inhibitor of the stress-activated kinase p38a, and was nominated as potential disease-modifying drug for rheumatoid arthritis (RA). Purposeful degradation experiments performed on this compound was analyzed by RP-HPLC with UV detection. Analysis of the solid-state photostability samples indicated a lack of mass balance with an assay value of 25% impurities totaling 18% by total area percent. Closer inspection of the sample revealed imdissolved material in the bottom of the volumetric flask. This case study focuses on the identification of the degradation product that resulted in the undissolved material and source of the lack of mass balance. 

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