Determination of melarsoprol in biological fluids by high-performance liquid chromatography and characterisation of two stereoisomers by nuclear magnetic resonance spectroscopy.
The analysis of melarsoprol in whole blood, plasma, urine and cerebrospinal fluid is described. Extraction was made with a mixture of chloroform and acetonitrile followed by back-extraction into phosphoric acid. A reversed-phase liquid chromatography system with ultraviolet detection was used. The relative standard deviation was 1% at concentrations around 10 mumol/l and 3-6% at the lower limit of determination (9 nmol/l in plasma, 93 nmol/l in whole blood, 45 nmol/l in urine and 10 nmol/l in cerebrospinal fluid). Melarsoprol is not a stable compound and samples to be stored for longer periods of time should be kept at -70 degrees C. Plasma samples can be stored at -20 degrees C for up to 2 months. Chromatography showed that melarsoprol contains two components. Using nuclear magnetic resonance spectroscopy the two components were shown to be diastereomers which slowly equilibrate by inversion of the configuration at the As atom.
Ericsson
O
O
Hospital Pharmacy, Huddinge University Hospital, Sweden.
Schweda
E K
EK
Bronner
U
U
Rombo
L
L
Fridén
M
M
Gustafsson
L L
LL
D000818:Animals; D001826:Body Fluids / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008549:Melarsoprol / Q000032:analysis* / Q000097:blood / Q000134:cerebrospinal fluid / Q000652:urine; D015203:Reproducibility of Results; D013237:Stereoisomerism; D014344:Trypanocidal Agents / Q000032:analysis* / Q000097:blood / Q000134:cerebrospinal fluid / Q000652:urine; D014347:Trypanosoma brucei gambiense; D014353:Trypanosomiasis, African / Q000097:blood / Q000134:cerebrospinal fluid / Q000188:drug therapy / Q000652:urine
D014344:Trypanocidal Agents; D008549:Melarsoprol