The results of the simulation study are given in Annex 3, For each brand the analytical results of the two batches are reported separately. For each batch the main findings are visualized in a graph, showing the level of active ingredient over time at various storage conditions. Colour of the solution and pH and oxygen are reported in separate tables, A summary of the results is given below.

Active ingredient

The stability results per batch, as shown in Annex 3, give a consistent pattern. An example is given in Figure 1. From this example of ergometrine injection it can be seen that the level of active ingredient in this product remains fairly constant when it is stored at 4-8°C in the dark; stability declines with increasing storage temperature. At 50°C in the dark the product is very unstable, with only 26% of the stated amount of active ingredient left after 12 months. When stored in the dark at 21-25°C, potency remains between 93-100% of the stated amount for 12 months. However, if kept in the light at the same temperature, potency decreases to 16% after 12 months. Storage for 24 months at 4-8°C and 21 °C in the dark result in potencies of 103 and 86% respectively.

For practical purposes the stability of each product can be characterized by looking at the level of active ingredient after 12 months storage at 4-8°C and at 30°C in the dark, and at 21-25°C in the light. These data are presented in Annex 4. Data referring specifically to the influence of light are summarized separately in Annex 5. The mean values per drug, as listed in Annex 4, are summarized in Table 3. The results are expressed both as percentage of the stated amount and as percentage of the initial amount, with 95% confidence limits.

Figure 1 Stability Of ergometrine Infection (E1, batch 0181189)

Table 3 Stability of injectable oxytocics

* Mean values (95% confidence limits)

Colour

For each sample of (methyl)ergometrine the colour of the solution on the dilution scale is given in Annex 3. The mean levels of active ingredient per degree of discolouration are summarized in Tables 4 and 5 and visualized in Figures 2 and 3. Maximum discolouration is represented by 1 on the dilution scale.

The correlation coefficient (r) between discolouration and level of active ingredient is 0.8487 for ergometrine (t=31.69, p<0.001) and 0.8730 for methylergometrine 0=35,35, p<0.001). The regression equation is y-15,54+(9.35)x for ergometrine and y=3.60+(10,35)x for methylergometrine. These lines have been included in Figures 2 and 3,

Oxygen content and pH

Oxygen content of the samples varied from 2.7-19.6 KPs for ergometrine and 2.9-13.6 KPs for methylergometrine. In five samples of ergometrine and two of methylergometrine the oxygen content exceeded the usual industrial standard of 4.7 KPs for products which are easily oxidizable.

The pH of the samples varied from 3,0-3.6. All samples complied with BP limits of pH 2.7-3.5 except two batches from one and the same manufacturer.

Table 4 Mean level of ergometrine per degree of discolouration

* As percentage of stated amount

Figure 2 Active ingredient per level of discolouration (ergometrine)

Table 5 Mean level of methylergometrine per degree of discolouration

* As percentage of stated amount

Figure 3 Active ingredient per level of discolouration (methylergometrine)