A Rapid HPLC Procedure for the Simultaneous Determination of Chloroquine, Monodesethylchloroquine, Diazepam, and Nordiazepam in Blood

Abstract

Chloroquine, monodesethylchloroquine, diazepam, and nordiazepam levels are simultaneously determined in whole blood or plasma by HPLC. Papaverine is used as internal standard, and the analysis is performed after protein-binding hydrolysis, absorption on Extrelut, and elution with diethyl ether/methylene chloride (70:30 v/v). UV detection is used at 343 nm for 12 min, then changed to 242 nm. There are two mobile phases with two flow rates. The procedure requires 30 min, is reproducible, sensitive (8-10 ng/mL for chloroquine and its metabolite, 4 ng/mL for diazepam and nordiazepam), and selective, especially towards other antimalarial agents and drugs like adrenaline or barbiturates, which may be used in chloroquine poisoning therapy. It can be used for pharmacokinetic studies, therapeutic control, to establish the diagnosis and prognosis of a chloroquine poisoning, and to follow and optimize treatment.

Transplacental Distribution of Chloroquine in Sheep

“…The lower placental transfer of the metabo lite could be explained by its more hydro philic character. In analogy with the bloodbrain barrier, lipophilicity seems to be the major determinant of transfer rate [11], Assuming that the effective concentration of chloroquine against chloroquine-sensitive Plasmodium is 50 ng/ml [12], present results suggest that a single administration of chlor oquine during labour is only a short-term protection for the newborn because the con centrations in the fetus are lower than 50 ng/ml after ± 3 days.…”

Development and Validation of an Hilic–MS/MS Method by One-Step Precipitation for Chloroquine in Miniature Pig Plasma

“…Chloroquine has a strongly basic tertiary amine group (Figure 1, pK a 10.47 [20]) that readily interacts with silanol groups in the stationary phase of RPLC columns, probably resulting in secondary retention and consequent broad peak shapes (>1 min). The C18 column was the most frequently used columns in previously published research [7][8][9][10][12][13][14] and we have investigated the peak shape and response of several C18 columns in the optimization process.…”

Analytical Methods on Determination in Pharmaceuticals and Biological Materials of Chloroquine as Available for the Treatment of COVID-19

“…C18 columns were preferred more than C8 to quantify CQ. The possible reason for this may be that CQ has a strong basic tertiary amine group, pK a 10.47 [25] that easily interacts with the silanol groups in the stationary phase of the RPLC columns.…”