Feasibility of amlodipine besylate, chloroquine phosphate, dapsone, phenytoin, pyridoxine hydrochloride, sulfadiazine, sulfasalazine, tetracycline hydrochloride, trimethoprim and zonisamide in SyrSpend(®) SF PH4 oral suspensions.

The objective of this study was to evaluate the feasibility of 10 commonly used active pharmaceutical ingredients (APIs) compounded in oral suspensions using an internationally used suspending vehicle (SyrSpend(®) SF PH4 liquid): (i) amlodipine, (as besylate) 1.0mg/mL; (ii) chloroquine phosphate,15.0 mg/mL; (iii) dapsone, 2.0 mg/mL; (iv) phenytoin, 15.0 mg/mL; (v) pyridoxine hydrochloride, 50.0 mg/mL; (vi) sulfadiazine, 100.0 mg/mL; (vii) sulfasalazine, 100.0 mg/mL; (viii) tetracycline hydrochloride, 25.0 mg/mL; (ix) trimethoprim, 10.0 mg/mL; and (x) zonisamide, 10.0 mg/mL. All suspensions were stored both at controlled refrigeration (2-8 °C) and controlled room temperature (20-25 °C). Feasibility was assessed by measuring the percent recovery at varying time points throughout a 90-day period. API quantification was performed by high-performance liquid chromatography (HPLC-UV), via a stability-indicating method. Given the percentage of recovery of the APIs within the suspensions, the expiration date of the final products (API+vehicle) was at least 90 days for all suspensions with regard to both the controlled temperatures. This suggests that the vehicle is stable for compounding APIs from different pharmacological classes.

Split calibration curve: an approach to avoid repeat analysis of the samples exceeding ULOQ.

BACKGROUND: The current practice of using calibration curves with narrow concentration ranges during bioanalysis of new chemical entities has some limitations and is time consuming. In the present study we describe a split calibration curve approach, where sample dilution and repeat analysis can be avoided without compromising the quality and integrity of the data obtained. RESULTS: A split calibration curve approach is employed to determine the drug concentration in plasma samples with accuracy and precision over a wide dynamic range of approximately 0.6 to 15,000 ng/ml for dapsone and approximately 1 to 25,000 ng/ml for cyclophosphamide and glipizide. A wide dynamic range of concentrations for these three compounds was used in the current study to construct split calibration curves and was successfully validated for sample analysis in a single run. CONCLUSION: Using this method, repeat analysis of samples can be avoided. This is useful for the bioanalysis of toxicokinetic studies with wide dose ranges and studies where the sample volume is limited.

Dapsone for autoimmune thrombocytopenic purpura.

Twenty-one human immunodeficiency virus (HIV)-free and six HIV-infected adults with autoimmune thrombocytopenic purpura (AITP) were treated with dapsone (100 mg/day). A response was observed in 13 patients (median platelet count before 25 x 10(9)/L, range 3-49; after 109 x 10(9)/L, range 69-241). Thrombocytopenia recurred in four of the responders in whom dapsone was discontinued. No response was observed in 12 patients. Dapsone had to be withdrawn after two weeks of treatment in the remaining two patients and after six to eight weeks in three other patients due to intolerance. No serious hematological complications were observed. These results confirm that dapsone is a safe, inexpensive, and effective treatment of AITP.