Speciation of antimony in injectable drugs used for leishmaniasis treatment (Glucantime®) by HPLC-ICP-MS and DPP.

Meglumine antimonate is the active of Glucantime® used for the treatment of leishmaniasis, a tropical disease caused by parasitic protozoa, and it is estimated that 12 million people worldwide are affected. This drug mainly contains Sb(V) under the form of an organic complex with N-methylglucamine (NMG). During the synthesis of this molecule, traces of Sb(III) may be present, also probably complexed. Due to the fact that Sb(III) is considered more toxic than Sb(V), it is important to evaluate the Sb(III) concentration in the drug samples. In the literature, very different concentrations for residual concentrations of Sb(III) in the drug ampoules are found. Therefore, to have a true insight of antimony speciation, two independent analytical methods were developed in this work. We used an anion exchange method coupled with inductively coupled plasma mass spectrometry (ICP-MS) which was cross-referenced with an electrochemistry method (differential pulse polarography (DPP)) that could be used for routine analysis on the production site. To obtain Sb species in detectable forms, the complexes between Sb species and NMG need to be broken. This was obtained by diluting samples in hydrochloric acid in deaerated conditions to avoid Sb redox reactions. For the two analytical methods, the HCl concentration was optimized to obtain simultaneously a complete destruction of the complexes as well as limited redox reactions for Sb(V) and Sb(III) released species. For high-performance liquid chromatography (HPLC)-ICP-MS, a dilution with 5 M HCl gives the better results. The side reaction is an oxidation of Sb(III) which can be limited by the removal of oxygen. When DPP is used, the major problem is the reduction of Sb(V) which is present in high amount in the samples. Working with 0.6 M HCl allows this problem to be minimized. When applied to different lots of Glucantime®, Sb(III) concentration values are in good agreement for the two analytical methods, with, for HPLC-ICP-MS, the advantage of the simultaneous detection of both Sb redox species.

Dimensions of the left ventricle, atrium, and aortic root in pregnancy-induced hypertension.

Chronic hypertension induces changes in the structure of the left ventricle, atrium, and aortic root. However, the effects of transient hypertension are unclear. Pregnancy-induced hypertension (PIH) offers a natural and spontaneous model of this condition. Using M-mode echocardiography, we studied 95 consecutive patients with PIH, who were compared with 83 normal pregnant women (NPW). We evaluated diastolic diameter (DD), systolic diameter (SD), septal thickness (ST), posterior wall thickness (PWT), shortening fraction (SF), relative wall thickness (RWT), left ventricular mass index (LVMI), left atrial dimension (LAD), and aortic root dimension (ARD). Patients with PIH had higher ST (9.98 +/- 1.47 mm v 8.96 +/- 1.43 mm, P < .000), PWT (9.28 +/- 1.48 mm v 8.55 +/- 1.35 mm, P < .000), LVMI (107.65 +/- 27.87 g/m2 v 92.38 +/- 17.99 g/m2, P < .000), and RWT (0.406 +/- 0.06 v 0.377 +/- 0.06 mm, P < .002). There were no significant differences in DD, SD, SF, LAD, and ARD. In conclusion, PIH increases the LVMI due to an increase in the ST and PWT. The dimensions of the left ventricle, left atrium, and aortic root do not change.

Left ventricular function impairment in pregnancy-induced hypertension.

The changes induced by transient hypertension on cardiac structure and function are unclear. Pregnancy-induced hypertension offers a natural and spontaneous model of this condition. To assess the potential of echocardiographic Doppler to unmask left ventricular function impairment, we studied 28 women aged 26.4 +/- 7.2 years with pregnancy-induced hypertension defined as blood pressure higher than 140/90 mm Hg in the third trimester of pregnancy without a history of hypertension. Twenty normal pregnant women, aged 27.5 +/- 6.4 years, were the controls. Left ventricular diastolic diameter, fractional shortening, E velocity, A velocity, E/A ratio, isovolumetric relaxation time (IRT), isovolumetric contraction time (ICT), ejection time (ET), and the combined index of myocardial performance (Tei index = IRT + ICT/ET), were calculated by echocardiography Doppler 2 to 4 days postpartum. There were statistically significant differences between groups in the following parameters: E/A ratio: 1.3 +/- 0.3 in pregnancy-induced hypertension v 1.5 +/- 0.3 in normal pregnant women (P < .05), IRT: 104 +/- 14 msec v 84 +/- 7 msec (P < .000), and the Tei index: 0.51 +/- 0.15 v 0.35 +/- 0.04 (P < .00), respectively. According to this data pregnancy-induced hypertension evaluated 2 to 4 days after delivery showed left ventricular dysfunction, mainly diastolic. The IRT and the Tei index are the most useful echocardiographic parameters to unmask left ventricular dysfunction in pregnancy-induced hypertension.

Left ventricular geometry in pregnancy-induced hypertension.

The changes induced by transient hypertension upon cardiac geometry (G) are unclear. Pregnancy-induced hypertension (PIH) offers a natural and spontaneous model of this condition. To assess geometric changes according to two-dimensionally guided M-mode echocardiography, we compared patients with PIH with normal pregnant women (NPW). Fifty-five women, aged 28.5 +/- 7.5 years, with PIH (defined as blood pressure >140/90 mm Hg in the third trimester of pregnancy and without a history of hypertension) were compared with 57 NPW aged 30.7 +/- 7.5 years. Left ventricular mass index (LVMI) (Devereux formula) and relative wall thickness (RWT) (Ganau formula) were calculated by means of echocardiography done in the left lateral decubitus 2 to 4 days postpartum. Subjects were considered to have: normal geometry (NG) if both LVMI and RWT fell below the mean +/- 1 SD or 2 SD; concentric hypertrophy (CH) if both were elevated; eccentric hypertrophy (EH) if LVMI was elevated and RWT was normal; and concentric remodeling (CR) if LVMI was normal and RWT was elevated. Comparisons were performed by the Student t test. Patients with PIH had higher LVMI (106 +/- 29.4 v 90.6 +/- 19.8 g/m2; P < .05) and RWT (0.41 +/- 0.07 v 0.38 +/- 0.05; P < .05). Considering the mean +/- 1 SD of NPW as the limit of normality the G pattern was NG in 26 (47%) and abnormal in 29 (53%), of which 14 (25.5%) had EH, 11 (20%) had CR, and four (7%) had CH. If we considered the mean +/- 2 SD, the G pattern was NG in 46 (84%) and abnormal G in nine (16%), EH in four (7%), CR in three (5%), and CH in 2 (4%). According to these data, women with PIH had higher LVMI and RWT compared with NPW. The most frequent abnormal G patterns were EH and CR.