Accessibility and potency of uterotonic drugs purchased by simulated clients in four districts in India.

BACKGROUND: Surveillance of drug quality for antibiotics, antiretrovirals, antimalarials and vaccines is better established than surveillance for maternal health drugs in low-income countries, particularly uterotonic drugs for the prevention and treatment of postpartum hemorrhage. The objectives of this study are to: assess private sector accessibility of four drugs used for uterotonic purposes (oxytocin, methylergometrine, misoprostol, valethamate bromide); and to assess potency of oxytocin and methylergometrine ampoules purchased by simulated clients. METHODS: The study was conducted in Hassan and Bagalkot districts in Karnataka state and Agra and Gorakhpur districts in Uttar Pradesh state. A sample of 877 private pharmacies was selected (using a stratified, systematic sampling with random start), among which 847 were successfully visited. The target sample size for assessment of accessibility was 50 pharmacies per drug, per district. The target sample size for potency assessment was 100 purchases each of oxytocin and methylergometrine across all districts. Successful drug purchases varied by state. RESULTS: In Agra and Gorakhpur, 90%-100% of visits for each of the drugs resulted in a purchase. In Bagalkot and Hassan, only 29%-52% of visits for each drug resulted in a purchase. Regarding potency, the percent of active pharmaceutical ingredient was assessed using United States Pharmacopeia monograph #33 for both drugs; 193 and 188 ampoules of oxytocin and methylergometrine, respectively, were assessed. The percent of oxytocin ampoules outside manufacturer specification ranged from 33%-40% in Karnataka and from 22%-50% in Uttar Pradesh. In Bagalkot and Hassan, 96% and 100% of the methylergometrine ampoules were outside manufacturer specification, respectively. In Agra and Gorakhpur, 54% and 44% were outside manufacturer specification, respectively. CONCLUSION: Private sector accessibility of uterotonic drugs in study districts in Karnataka warrants attention. Most importantly, interventions to assure quality oxytocin and particularly methylergometrine are needed in study districts in both states.

Impact of temperature exposure on stability of drugs in a real-world out-of-hospital setting.

STUDY OBJECTIVE: The aim of this study is to determine the content of 5 important emergency medical services (EMS) drugs after being stored at the recommended refrigerated temperature, room temperature, or in an emergency physician transport vehicle operating under real-world working conditions. METHODS: Adrenaline hydrochloride, cisatracurium besylate, lorazepam, methylergonovine maleate, and succinylcholine chloride were stored for 1 year under the 3 conditions. For each storage condition, samples of the drugs were taken after 1, 2, 3, and 4 weeks and after 2, 4, 6, 8, 10, and 12 months. For adrenaline hydrochloride, however, the samples were taken after 1, 2, 4, 6, 8, 10, and 12 months. The samples were analyzed with a validated high-performance liquid chromatography assay. A drug was considered stable if its content was above 90%. RESULTS: Adrenaline hydrochloride and methylergonovine maleate remained stable for 1 year at room temperature and in the emergency physician transport vehicle. At room temperature and in the emergency physician transport vehicle, lorazepam became unstable within 4 weeks. Succinylcholine chloride was stable for 2 months at room temperature and for 1 month in the emergency physician transport vehicle. Cisatracurium besylate became unstable within 4 months at room temperature. However, it remained stable for 4 months in the emergency physician transport vehicle. CONCLUSION: When stored at room temperature or in the emergency physician transport vehicle, lorazepam became unstable within weeks, whereas succinylcholine chloride and cisatracurium besylate became unstable within months. Adrenaline hydrochloride and methylergonovine maleate remained stable for several months, even under room temperature and emergency physician transport vehicle conditions. Thus, real-world EMS working conditions pose challenges for maintaining optimal efficacy of these important EMS drugs.

Instability of (methyl)ergometrine in tropical climates: an overview.

Parenteral ergometrine is widely used for the prevention and treatment of excessive uterine bleeding following birth. Unfortunately, in tropical climates it is often found to contain very little active ingredient: only 32 of 100 field samples from Bangladesh, Gambia, Malawi, Yemen and Zimbabwe contained 90-110% of the amount of active ingredient stated on the label, and 34 contained less than 60%. In this paper the results of nine studies, of which eight were initiated and coordinated by WHO, are reviewed to formulate answers to the following questions: (1) what is the extent of the problem of low potency of ergometrine in tropical climates; (2) is the problem due to instability or low initial quality, or both; (3) which practical measures can assure the quality of injectable ergometrine; and (4) are there any alternative drugs which are more stable? Injectable ergometrine is very unstable under tropical conditions and particularly if stored unrefrigerated and exposed to light, when it may loose up to 20% of its potency per month. However, there are differences between brands. Practical measures to assure the quality of injectable ergometrine therefore include a careful supplier selection and refrigerated storage. Ergometrine injection should always be protected from light until given to the patient. Loss of active ingredient can easily be detected by regular visual checks of the colour of the solution. Any discoloration implies that the solution contains less than 90% of the stated amount of active ingredient, and should not be used. Methylergometrine is no more stable than ergometrine. Parenteral oxytocin is more stable than both ergometrine and methylergometrine injection. Oral and buccal dosage forms are less stable than injections. In view of the better stability in tropical climates, similar cost, fewer side effects and comparative efficacy, parenteral oxytocin, rather than parenteral ergometrine, is the drug of choice in the prevention and treatment of postpartum haemorrhage.

[Methylergometrine Maleate Reference Standard (Control 891) of National Institute of Hygienic Sciences].

The raw material of methylergometrine maleate was examined for the preparation of the "Methylergometrine Maleate Reference Standard". Analytical data obtained were as follows: melting point, 181.7 degrees C; ultraviolet spectrum, lambda max = 313 nm; absorbance, E1%1cm (313 nm) = 181.3; infrared spectrum, 3406, 2962, 2928, 1645, 1574 cm-1; thin-layer chromatography, 6 impurities were detected; high-performance liquid chromatography, no impurities were detected; loss on drying, 0.02%; optical rotation, [alpha]20D = + 44.04 degrees; assay, 99.5% against Ergometrine Maleate Reference Standard (Control 755). Based on the above results, this raw material was authorized to be the Reference Standard of the National Institute of Hygienic Sciences.