The opioid that produces a metabolite called morphine-6-glucuronide (M6G), which significantly contributes to its extended analgesic effect, is morphine.

- Morphine undergoes extensive metabolism in the liver, primarily through conjugation with glucuronic acid.
- This process forms two main metabolites: morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G).
- Among these, M6G is pharmacologically active and possesses potent analgesic properties.
- In fact, M6G has a higher affinity for the mu-opioid receptor than morphine itself, which contributes to prolonged and enhanced analgesic effects.

The presence of M6G is particularly important in patients with renal impairment, as this metabolite is primarily excreted by the kidneys. Accumulation of M6G in such cases can lead to prolonged opioid effects and increased risk of toxicity.

In contrast, other opioids in the list do not produce this specific active metabolite:
- Fentanyl is metabolized mainly by CYP3A4 to inactive metabolites.
- Codeine is metabolized to morphine but does not produce M6G directly.
- Tramadol works through a combination of weak mu-opioid agonism and serotonergic/noradrenergic pathways and does not produce M6G.

Therefore, the unique contribution of morphine-6-glucuronide to the analgesic profile is a characteristic feature of morphine therapy.

Reference: Goodman & Gilman's The Pharmacological Basis of Therapeutics, 13th Edition, Chapter 15: Opioid Analgesics and Antagonists / Page 485