Temperature stability of oxytocin ampoules labelled for storage at 2°C-8°C and below 25°C: an observational assessment under controlled accelerated and temperature cycling conditions.

INTRODUCTION: Oxytocin, administered via injection, is recommended by WHO for the prevention and treatment of postpartum haemorrhage. However, the susceptibility of oxytocin injection to thermal degradation has led WHO and UNICEF to recommend cold-chain storage of all oxytocin products. Nevertheless, some oxytocin products supplied to the global market are labelled for storage at ≤25°C, often with a shorter shelf-life relative to products labelled for refrigeration. Differences in labelled storage requirements can lead to uncertainties among stakeholders around the relative stability of oxytocin products and specifically whether ≤25°C products are more resistant to degradation. Such confusion can potentially influence policies associated with procurement, distribution, storage and the use of oxytocin in resource-poor settings. OBJECTIVES: To compare the stability of oxytocin injection ampoules formulated for storage at ≤25°C with those labelled for refrigerated storage. DESIGN: Accelerated and temperature cycling stability studies were performed with oxytocin ampoules procured by the United Nations Population Fund (UNFPA) from four manufacturers. METHOD: Using oxytocin ampoules procured by UNFPA, accelerated stability (up to 120 days) and temperature cycling (up to 135 days between elevated and refrigerated temperatures) studies were performed at 30°C, 40°C and 50°C. Oxytocin content was quantified using a validated HPLC-UV method. RESULTS: All ampoules evaluated exhibited similar stability profiles under accelerated degradation conditions with the exception of one product formulated for ≤25°C storage, where the rate of degradation increased at 50°C relative to other formulations. Similar degradation trends at elevated temperatures were observed during temperature cycling, while no significant degradation was observed during refrigerated periods of the study. CONCLUSION: Oxytocin ampoules formulated for non-refrigerated storage demonstrated comparable stability to those labelled for refrigerated storage and should not be interpreted by stakeholders as offering a more stable alternative. Furthermore, these products should not be procured for use in territories with high ambient temperatures, where all oxytocin injection products should be supplied and stored under refrigerated conditions.

Rapid method for the quantitative determination of efavirenz in human plasma.

A pharmacokinetic interaction study between efavirenz (EFV), a non-nucleoside reverse transcriptase inhibitor used in the treatment of HIV-1 infection, and an African traditional medicine, African potato in human subjects was undertaken. This necessitated the development and validation of a quantitative method for the analysis of EFV in plasma. A simple mobile phase consisting of 0.1M formic acid, acetonitrile and methanol (43:52:5) was pumped at a low flow rate of 0.3 ml/min through a reverse phase Phenomenex Luna C(18) (2) (5 microm, 150 mm x 2.0mm i.d.) column maintained at 40 degrees C. Diclofenac sodium was used as an internal standard (IS) and EFV and IS were monitored at 247 nm and 275 nm, respectively. A simple and rapid sample preparation involved the addition of mobile phase to 100 microl of plasma to precipitate plasma proteins followed by direct injection of 10 microl of supernatant onto the column. The procedures were validated according to international standards with good reproducibility and linear response (r=0.9990). The intra- and inter-day accuracies were between 12.3 and 17.7% at the LLOQ and between -5.8 and 9.1% for the QC samples. The intra- and inter-day precision of EFV determinations were 5.1 or less and 7.2% RSD or less, respectively across the entire QC concentration range. Mean recovery based on high, medium and low quality control standards ranged between 92.7 and 94.1% with %RSD values better than 3%. Plasma samples were evaluated for short-term (ambient temperature for 6h) and long-term (-10+/-2 degrees C for 60 days) storage conditions and were found to be stable. The method described is cost-effective and has the necessary accuracy and precision for the rapid quantitative determination of EFV in human plasma.

Effect of African potato (Hypoxis hemerocallidea) on the pharmacokinetics of efavirenz.

PURPOSE: The purpose of this study was to evaluate the effect of the African potato (AP) on the pharmacokinetics of efavirenz. METHODS; A single-dose, two-phase sequential study was conducted over 31 days in 10 healthy volunteers. On day 1 of the study, volunteers were administered a 600 mg efavirenz tablet, and blood samples were collected before dosing and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 18, 24, 36 and 48 hours after dosing. From day 16, a traditionally prepared AP decoction was administered daily until day 30. On day 29, volunteers were administered a single 600 mg dose of efavirenz, as was done on day 1. Plasma samples were harvested immediately after blood sample collection and frozen at -80 degrees C until assayed. Plasma concentrations of efavirenz were determined by a validated high performance liquid chromatography (HPLC) method with UV detection, and pharmacokinetic parameters were calculated. Geometric mean ratios of C(max) and AUC(0-48) of efavirenz before and after co-administration of 14 successive daily doses of AP were compared. RESULTS: All subjects completed the study. The geometric mean ratios of C(max) and AUC(0-48) were 97.30 and 102.82 with corresponding 90% confidence intervals (CIs) of 78.81 - 120.14 and 89.04 - 118.80, respectively. CONCLUSION: Pharmacokinetic data generated during this study indicated that AP did not significantly alter the pharmacokinetics of efavirenz. Hence, co-administration of AP is unlikely to affect the clinical usage of efavirenz.