Yes! In general, you cannot bring a drug to market without being able to measure it in blood reliably. But those tests are often not available in eg a rural hospital. This field is therefore a real interplay between doctors, statistici an/software engineers, and bio-assay manufacturers.

Now for illegal designer drugs, that is a completely different ball game. They may even be built to evade detection.

Some drugs are!

Drugs that work with a single dose for everyone are more convenient. Yes, paracetamol 1g tablet may give lower concentrations in someone weighing 140kg vs 70kg, but these drugs are safe and effective over a wide range of concentrations.

Some drugs have a more narrow therapeutic range. We either adapt the dose by bodyweight (paracetamol for children is a prime example!), but can adapt to many many more covariates. Even race can play a role, with some mutations increasing drug metabolism being less prevalent in whites, so more risk of overdose. And sometimes, it is not the dose but the frequency that is adapted (1g 2 times vs 3 times per day)

In some cases, no covariates exist. You either measure concentration in the blood, or you measure the effect (eg drugs for sedating during surgery).

Sure, it would be more optimal to also dose paracetamol that way. Dose high,measure concentration in blood and adapt. You would get faster pain relief with lower risk. But would you come to hospital and pay a team of doctors/engineers to do that, for a simple headache?

That was the question I answered with my PhD: is all that hastle worth it? For some life saving drugs with strong side effects and very variable metabolism, it is.

I did my PhD on this, but for living patients ;)

As you say, there are many factors at play, most importantly distribution volume and drug elimination rate. For all of these factors, you can estimate the typical value and the between-individual variability in the population. We call this a population pharmacokinetic model.

With just a single concentration, you assume this person is a "typical individual". You can back-calculate (based on time of death and time of taking the drug) what the dosage typically could have been. You need the administration time though, the time of death, and you better hope the drug concentration remained stable between time of death and time of autopsy. In clinical studies, blood samples are often stored in solid co2 (-80C), and for good reason.

Using the known variability in the population, you can also give a confidence range for your initial dose prediction. You can make predictions more precise by adding information. Bodyweight influences likely drug distribution volume. A second drug (with known dosage and administration time) could help you too.

Usually, this technique is done for drugs that need to be in a precise concentration range. Give a dose, measure concentration, estimate blood volume and calculate the optimal dose for that patient. We call this Model Informed Precision Dosing: MIPD. You can apply the same in autopsies, but I doubt it is routinely applied. Cool question!