Method for the direct detection and/or quantification of at least one compound with a molecular weight of at least 200

A method for analyzing a pharmaceutical composition comprising at least one phosphorus containing compound having a molecular weight of at least 200 daltons, wherein the amount of the at least one phosphorus containing compound in the pharmaceutical compostions is above 70% by weight,

• wherein the method comprises quantifying the phosphorus containing compound together with its impurities, wherein
• the at least one phosphorus containing compound is selected from:
• (a) a bisphosphonate or polyphosphonate;
• (b) a hexametaphosphate;
• (c) a C3-C7 cycloalkyl substituted compound with at least two —R group wherein each —R group is —OH, —OP(O)(OH)2 or —P(O)(OH)2, and wherein at least two —R groups are independently selected from —P(O)(OH)2 and —OP(O)(OH)2 and said C3-C7 cycloalkyl is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl;
• (d) ions or salts thereof;
• or,
• (e) a combination thereof;
• and,
• wherein said method comprises:
• 1) preparing at least one standard sample of a phosphorus containing compound to be analyzed;
• 2) preparing a test sample of the composition containing the at least one phosphorus containing compound, wherein the process to prepare said sample comprises at least partially or totally dissolving said composition to form a solution or a slurry containing the compound, without any sample pretreatment apart from diluting the test sample:
• 3) introducing the at least one standard sample together or sequentially with the test sample into a stream of a solvent system, wherein the solvent system is a polar solvent comprising potassium hydroxide (KOH) or a solvent mixture comprising at least one polar solvent comprising potassium hydroxide (KOH);
• and passing the samples through a single anion-exchange chromatography column containing particles of a polystyrene cross-linked with divinylbenzene polymer resin, wherein the column is essentially filled of the cross-linked polymer particles in a stationary phase while maintaining the pressure of the system in the anion-exchange chromatography column between 5 and 1500 atm;
• and,
• 4) identifying the retention time and/or quantifying the intensity of the signal of the at least one phosphorus containing compound when the samples are eluted from the anion-exchange chromatography column.