TY - JOUR
T1 - Identification and characterization of crystalline and amorphous HM-PAO fractions
T2 - Their relevance for preparation of the 99mTc-d,l-HM-PAO brain perfusion imaging agent
AU - Feinstein-Jaffe, Irene
AU - Azoury, Reuven
AU - Bernstein, Joel
AU - Sarma, J. A.R.P.
AU - Boazi, Miriam
PY - 1990/1/1
Y1 - 1990/1/1
N2 - The 99mTc d,l-HM-PAO complex has been shown to be an effective complex for cerebral perfusion imaging. Fractional crystallizations of the crude HM-PAO reduction product yield several fractions of varying crystallinity and isomeric purity. The presence of these mixed fractions greatly hinders the efficient separation of d,l and meso diastereomers and lowers the overall yield of the d,l isomer. The measurement of the respective melting points does not reveal accurately the composition of these fractions as regards the degree of meso impurity. Therefore these fractions have been identified and characterized by mass spectroscopy, optical and scanning electron microscopy, differential scanning calorimetry, NMR spectroscopy, and powder X-ray diffraction. Single crystals of pure d,l-HM-PAO (m.p. 129.8°C) have been isolated as well as pure meso HM-PAO (m.p. 144°C). A lower melting point fraction (117-118°C) is present in large amounts. This is a mixture of d,l and meso HM-PAO diastereomers and contains a significant amount of amorphous phase. We propose that this amorphous phase is derived from inefficient dissolution of meso HM-PAO in the crude reduction reaction mixture. This results in mixed meso-d,l fractions which thereafter are very difficult to separate. These observations regarding amorphous and crystalline phases in isomeric mixtures have general implications regarding ligands used in the preparation of radiopharmaceuticals, specifically 99mTc complexes as brain imaging agents, where stereochemical purity invariably plays significant role.
AB - The 99mTc d,l-HM-PAO complex has been shown to be an effective complex for cerebral perfusion imaging. Fractional crystallizations of the crude HM-PAO reduction product yield several fractions of varying crystallinity and isomeric purity. The presence of these mixed fractions greatly hinders the efficient separation of d,l and meso diastereomers and lowers the overall yield of the d,l isomer. The measurement of the respective melting points does not reveal accurately the composition of these fractions as regards the degree of meso impurity. Therefore these fractions have been identified and characterized by mass spectroscopy, optical and scanning electron microscopy, differential scanning calorimetry, NMR spectroscopy, and powder X-ray diffraction. Single crystals of pure d,l-HM-PAO (m.p. 129.8°C) have been isolated as well as pure meso HM-PAO (m.p. 144°C). A lower melting point fraction (117-118°C) is present in large amounts. This is a mixture of d,l and meso HM-PAO diastereomers and contains a significant amount of amorphous phase. We propose that this amorphous phase is derived from inefficient dissolution of meso HM-PAO in the crude reduction reaction mixture. This results in mixed meso-d,l fractions which thereafter are very difficult to separate. These observations regarding amorphous and crystalline phases in isomeric mixtures have general implications regarding ligands used in the preparation of radiopharmaceuticals, specifically 99mTc complexes as brain imaging agents, where stereochemical purity invariably plays significant role.
UR - http://www.scopus.com/inward/record.url?scp=0025384975&partnerID=8YFLogxK
U2 - 10.1016/0022-0248(90)90609-O
DO - 10.1016/0022-0248(90)90609-O
M3 - Article
AN - SCOPUS:0025384975
SN - 0022-0248
VL - 100
SP - 68
EP - 74
JO - Journal of Crystal Growth
JF - Journal of Crystal Growth
IS - 1-2
ER -