The stability of tigecycline in fresh and aged ca-MHB with and without adding stabilizing agents was investigated (Table
1). In 7-day-old, non-stabilized ca-MHB, a recovery of 80.1% was found within 24 h. Conversely, in fresh, non-stabilized ca-MHB, 99.6% tigecycline was measured. Moreover, tigecycline degraded already to a remaining concentration of 89.7% using the same ca-MHB solution 1 day after preparation. The stabilizing agents had various effects: In ca-MHB
aa0.3%, tigecycline degraded rapidly and only 4.7% remained in a freshly prepared solution within 24 h. In ca-MHB
7days_p2%, we observed a stabilizing effect and 97.1% were recovered. Moreover, the combination of 6% pyruvate and 0.3% ascorbic acid, as recommended by
Jitkova et al. [
2], was inferior to 2% pyruvate alone, and a remaining concentration of 97.2%, if freshly prepared, and 95.1% in ca-MHB
7days_p6% + aa0.3% was measured. Furthermore, the stability of tigecycline was investigated in ca-MHB
7days_RT and the age dependency of tigecycline stability was even more observable. In MHB
7days_RT with 2% pyruvate, a remaining concentration of 87.8% was measured (Table
1), whereas in non-stabilized ca-MHB
7days_RT, only 27.9% tigecycline were recovered. As described above, the combination of 0.3% ascorbic acid and 6% pyruvate was not superior to pyruvate alone so that pyruvate was increased to 6% to enhance tigecycline stability in MHB
7days_RT and 97.1% could be recovered after 24 h.
Table 1
Tigecycline concentrations expressed as a relative percentage of the initially measured tigecycline concentrations (= 100%) in cation-adjusted Mueller Hinton broth (ca-MHB) with or without supplementation, incubated in the dark at 37 °C over 24 h stored in Eppendorf vial racks. Ca-MHB age of 0 days was defined as ca-MHB preparation less than 12 h before the experiment started. Ca-MHB was stored up to 7 days at 4 °C or at room temperature. Storage conditions and age refer to Ca-MHB without supplements in absence of tigecycline before the 24 h incubation period with tigecycline with and without supplements at 37 °C was initiated
Ca-MHB | 0 | | 99.6 | 94.5–103.5 | 0.412 |
1 | 4 °C | 89.7 | 87.4–94.8 | 0.400 · 10−2 |
7 | 4 °C | 80.1 | 82.8–75.6 | 2.44 · 10−6 |
7 | Room temperature | 27.9 | 25.9–30.0 | 2.2 · 10−16 |
Ca-MHB + 0.3% ascorbic acid | 0 | | 4.7 | 3.5–5.1 | 2.47 · 10−6 |
Ca-MHB + 2% pyruvate | 0 | | 98.8 | 97.0–100.3 | 9.20 · 10−2 |
7 | 4 °C | 97.1 | 96.4–99.6 | 8.40 · 10−2 |
7 | Room temperature | 87.8 | 86.6–88.8 | 1.69 · 10−11 |
Ca-MHB + 0.3% ascorbic acid+6% pyruvate | 0 | | 97.2 | 93.4–100.2 | 0.079 |
7 | 4 °C | 95.1 | 91.3–97.3 | 6.40 · 10−2 |
Ca-MHB + 6% pyruvate | 7 | Room temperature | 97.1 | 95.6–98.5 | 1.1 · 10−2 |