Assay for lanthanum hydroxycarbonate

Abstract

An assay for analytically determining the amount of an impurity in a solid sample is provided. This X-ray diffraction method preferably uses the Rietveld refinement.

1 . A method of assaying the purity of a rare earth compound having at least one known impurity, wherein at least one of the salt or impurity is a compound that disassociates in aqueous media, comprising: 
 (i) obtaining an X-ray diffraction pattern of the salt;    (ii) obtaining a plurality of reference samples containing the impurity or impurities;    (iii) obtaining a plurality of X-ray diffraction patterns of the reference samples; and    (iv) performing Rietveld analysis on the X-ray diffraction patterns to obtain: 
 the detection limit, minimum quantitation limit (MQL), and/or upper analytical limit from the reference samples and  
 the predicted impurity concentration value from the rare earth compound pattern.  
   
   
   
       2 . A method of assaying the concentration of lanthanum hydroxycarbonate in a lanthanum carbonate composition comprising: 
 (i) obtaining an X-ray diffraction pattern of the lanthanum carbonate;    (ii) obtaining a plurality of reference samples containing the lanthanum hydroxycarbonate;    (iii) obtaining a plurality of X-ray diffraction patterns of the reference samples; and    (iv) performing a Rietveld analysis on the X-ray diffraction patterns to obtain: 
 the detection limit, minimum quantitation limit (MQL), and/or upper analytical limit from the reference samples and  
 the predicted percent of lanthanum hydroxycarbonate.  
   
   
   
       3 . The method of  claim 1 , further comprising: 
 (v) classifying the predicted concentrations as: 
 below the detection limit,  
 between the detection limit and the MQL,  
   between the MQL and upper analytical limit, and 
 greater than the upper analytical limit;  
   (vi) for samples having a predicted concentration between the detection limit and the MQL, performing a visual analysis of the XRPD patterns; and    (ix) optionally reporting purity or impurity level.    
   
   
       4 . The method of  claim 1 , wherein both the rare earth compound and the impurity disassociate in an aqueous media to the same measurable degradants.  
   
   
       6 . The method of  claim 1 , wherein the rare earth compound is a lanthanum carbonate, lactate, acetate, or citrate.  
   
   
       7 . The method of  claim 6 , wherein the lanthanum salt is La 2 (CO 3 ) 3 .xH 2 O, wherein x has a value from 0 to 10.  
   
   
       8 . The method of  claim 7 , wherein the impurity is La(CO 3 )OH.  
   
   
       9 . The method of  claim 8 , wherein the impurity is a combination of La(CO 3 )OH form (I) and form (II).  
   
   
       10 . The method of  claim 1 , wherein the X-ray diffraction pattern from the lanthanum compound is obtained in triplicate.  
   
   
       11 . The method of  claim 1 , wherein X-ray diffraction patterns are obtained for at least 5 reference samples.  
   
   
       12 . The method of  claim 11 , wherein X-ray diffraction patterns are obtained for at least 20 reference samples.  
   
   
       13 . The method of  claim 1 , wherein the X-ray diffraction pattern is obtained by a two theta continuous scan at approximately 1°/min.  
   
   
       14 . The method of  claim 1 , further comprising visually determining if the impurity is present based on the presence of X-ray diffraction peaks characteristic of the impurity.  
   
   
       15 . A method of preparing lanthanum carbonate comprising: 
 (i) preparing a crude lanthanum carbonate;    (ii) subjecting the crude lanthanum carbonate to a purity assay comprising the steps: 
 (a) obtaining an X-ray diffraction pattern of the salt;  
 (b) obtaining a plurality of reference samples containing the impurity or impurities;  
 (c) obtaining a plurality of X-ray diffraction patterns of the reference samples; and  
 (d) performing Rietveld analysis on the X-ray diffraction patterns to obtain:  
 the detection limit, minimum quantitation limit (MQL), and/or upper analytical limit from the reference samples and  
 the predicted impurity concentration value from the rare earth compound pattern,  
   (iii) when the lanthanum carbonate contains lanthanum hydroxycarbonate above the limit of detection according to the assay of (ii), purifying the lanthanum carbonate and repeating step (ii).    
   
   
       16 . A pharmaceutical composition comprising lanthanum hydroxycarbonate form (I) characterized by an X-ray powder diffraction pattern having peaks at approximately 17.7°, 24.4°, and 30.3° two theta, wherein the lanthanum hydroxycarbonate content of the composition comprises at least 96% lanthanum hydroxycarbonate form (I).  
   
   
       17 . The pharmaceutical composition of  claim 16 , wherein the lanthanum hydroxycarbonate content of the composition comprises at least 98% lanthanum hydroxycarbonate form (I).  
   
   
       18 . The pharmaceutical composition of  claim 17 , wherein the lanthanum hydroxycarbonate content of the composition comprises at least 99% lanthanum hydroxycarbonate form (I).