Phosphates European Pharmacopoeia

Lange and Vejdelek reference more than 100 articles describing molybdate methods and 30 articles describing the methodology adapted in the European Pharmacopoeia were phosphate is first boxmd as ammonium phos-phomolybdate and thereafter reduced by stannous chloride. These articles were published in the 1930s to the 1970s. 

To 100 ml of the soluhon prepared (neutralized as prescribed if necessary), 4 ml of sulphomolybdic reagent R3 is added. The solution is shaken and 0.1 ml of stannous chloride solution R1 is added. A standard is prepared in the same manner using 2 ml of phosphate standard solution (5 ppm PO ) R and 98 ml of water R. After 10 min, compare the colors using 20 ml of each soluhon. Any color in the test soluhon should not be more intense than that in the standard. 

When rmder the conditions given the orthophosphate present in the sample soluhon reacts with the ammonium molybdate present in the sulphomolybdic reagent R3, yellow ammonium phosphomolybdate is formed in which MogOjo replaces each of the oxygen atoms in phosphate. 

Ammonium molybdate has the formula (NH4)sMo7024, but in the above reaction scheme, as well as in many other texts, it is presented as Mo04 for simplicity. The product is in some cases presented with the Brutto formula, 

If the ammonium phosphomolybdate concentration is too high, a yellow precipitate is formed. This has often been used deliberately in test procedures, but such methods suffer from tire reproducibility problems often encountered in tests based on precipitation. The environment must be acidic but the presence of nitric acid enhances the risk of ammonium phosphomolybdate precipitation, and hydrochloric acid gives a yellow precipitate of molybdic acid, H2M0O4. The presence of other ammonium salts also raises the risk of an unwanted ammonium phosphomolybdate precipitation provoked by the common ion effect. 

---

British Pharmacopoeia 2009 and European Pharmacopoeia 6.0 [3,7] specify fhat glimepiride is insoluble in water but it is soluble in dimethylforma-mide, slightly soluble in methylene chloride and very slightly soluble in methanol. Further, its log partition coefficient in octanol-water is 3.81, with log distribution coefficient in octanol-phosphate buffer pH 7.4 valued for 2.38 [8]. The value of glimepiride was found fo be 6.2 0.1 at 37 °C [2]. 

Aqueous parenteral preparations can contain trace amounts of heavy metal ions in concentrations sufficient to catalyze oxidative reactions. Aqueous parenterals are produced with the use of Water for injection, which complies with the limit test for heavy metals (European Pharmacopoeia, 2002). This is, however, no guarantee for exclusion of metal ions. Heavy metal contamination brought into the formulation by excipients is also a problem, especially for sugars, phosphate, and citrate (Nema et al., 2002). Heavy metals may also be extracted from the container by the preparation (European Pharmacopoeia, 2002 see Section 14.3). Moreover, trace elements like zinc, copper, manganese, and chromium constitute important components in several parenteral nutrition formulas (Trissel, 2001). 

---