Determination by capillary zone electrophoresis of mercaptopurine and thioguanine concentration in capsules for paediatric patients.
OBJECTIVE
Mercaptopurine monohydrate and thioguanine are two antineoplastic agents that inhibit purine metabolism. They are given by mouth in the treatment of acute leukaemias, usually for the maintenance of remission. In order to quantify these two antimetabolites into capsules for paediatric patients prepared in the pharmacy department, a capillary zone electrophoresis method (CZE) was developed.


METHODS
The equipment and reagents used included: a P/ACE 5000 capillary electrophoresis system, a 37 cm x 75 microm silica capillary, a 22.2 mM borate buffer (pH 9.0), 5 s high pressure injections, direct UV detection at 280 nm, run 20 kV. Hypoxanthine was used as an internal standard.


RESULTS
All compounds were separated in less than 3 min using a constant voltage of 20 kV. At a theoretical concentration of 100 microg/ml, the accuracy (average percentage of recovery = 98.9%, RSD = 0.45%, n = 6 for mercaptopurine and average percentage of recovery = 101.7%, RSD = 0.20%, n = 6 for thioguanine), the repeatability (RSD = 0.84%, n = 6 for mercaptopurine and RSD = 0.75%, n = 6 for thioguanine), the reproducibility (RSD = 0.58%, n = 18 for mercaptopurine and RSD = 1.55%, n = 18 for thioguanine) and the linearity of detection (range 50-150% of the studied concentration, r > 0.999 for mercaptopurine and r > 0.998 for thioguanine) were satisfactory. The capsule excipients did not interfere with quantification of the mercaptopurine or thioguanine peak.


CONCLUSIONS
The two antineoplastic agents could be assayed rapidly by the same capillary zone electrophoretic method with acceptable accuracy and precision. This method is suitable for routine control of capsules prepared for paediatric patients.
Georget
S
S
Centre Hospitalier Universitaire, Pharmacie Brabois Adultes, Vandoeuvre-les-Nancy, France.
Vigneron
J
J
May
I
I
Perrin
A
A
Hoffman
M A
MA
Hoffman
M
M
D000964:Antimetabolites, Antineoplastic / Q000032:analysis*; D002214:Capsules / Q000737:chemistry*; D002648:Child; D019075:Electrophoresis, Capillary / Q000379:methods*; D006801:Humans; D015122:Mercaptopurine / Q000032:analysis*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013866:Thioguanine / Q000032:analysis*
D000964:Antimetabolites, Antineoplastic; D002214:Capsules; D015122:Mercaptopurine; D013866:Thioguanine