MANGAFODIPIR TRISODIUM INJECTION, A NEW CONTRAST-MEDIUM FOR MAGNETIC-RESONANCE-IMAGING - DETECTION AND QUANTITATION OF THE PARENT COMPOUND MNDPDP AND METABOLITES IN HUMAN PLASMA BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY

Manganese(II) dipyridoxpl diphosphate (MnDPDP) is the active component of mangafodipir trisodium injection (Teslascan(R)); a new contrast me dium for magnetic resonance imaging. A high performance liquid chromat ography (HPLC) method was developed for the simultaneous determination of MnDPDP and its five major metabolites in human plasma, i.e. the de phosphorylation products MnDPMP (manganese(II) dipyridoxyl monophospha te) and MnPLED (manganese(II) dipyridoxyl ethylenediamine diacetate) a nd the corresponding substances obtained after transmetallation with z inc (ZnDPDP, ZnDPMP and ZnPLED). Heparinized blood samples from patien ts receiving mangafodipir trisodium injection were immediately mixed w ith solid trisodium phosphate dodecahydrate to obtain pH 10.0 +/- 0.2 in order to inhibit further in vitro dephosphorylation and transmetall ation. The plasma thus obtained was ultrafiltrated prior to HPLC analy sis, The chromatographic separation was obtained using a mixed-bed res in with both anion exchange and reversed-phase functions (OmniPac(TM) PAX-500) using isocratic elution and UV detection at 310 nm. With an i njection volume of 50 mu l, the limit of quantitation (LOQ) values wer e 0.8-2.3 mu M for the Mn compounds and 0.1-0.8 mu M for the Zn compou nds. The between-run accuracy of spiked plasma samples was in the rang e 97.5-106.7% with a precision in the range 3.1-9.0%. The best fit cal ibration curves were obtained using non-linear regression according to the equation Y = A + BXM in the concentration range from LOQ to 100 m u M. Long-term storage of spiked plasma samples for three months at - 20 degrees C demonstrated the required stability with recovery values within 85-115% of MnDPDP and its five metabolites. (C) 1997 Elsevier S cience B.V.